Trial watch: TLR3 agonists in cancer therapy
Toll-like receptor 3 (TLR3) is a pattern recognition receptor that senses exogenous (viral) as well as endogenous (mammalian) double-stranded RNA in endosomes. On activation, TLR3 initiates a signal transduction pathway that culminates with the secretion of pro-inflammatory cytokines including type I interferon (IFN). The latter is essential not only for innate immune responses to infection but also for the initiation of antigen-specific immunity against viruses and malignant cells. These aspects of TLR3 biology have supported the development of various agonists for use as stand-alone agents or combined with other therapeutic modalities in cancer patients. Here, we review recent preclinical and clinical advances in the development of TLR3 agonists for oncological disorders.
Abbreviations
cDC, conventional dendritic cell; CMT, cytokine modulating treatment; CRC, colorectal carcinoma; CTL, cytotoxic T lymphocyte; DC, dendritic cell; dsRNA, double-stranded RNA; FLT3LG, fms-related receptor tyrosine kinase 3 ligand; HNSCC, head and neck squamous cell carcinoma; IFN, interferon; IL, interleukin; ISV, in situ vaccine; MUC1, mucin 1, cell surface associated; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; polyA:U, polyadenylic:polyuridylic acid; polyI:C, polyriboinosinic:polyribocytidylic acid; TLR, Toll-like receptor
ABSTRACT
Toll-like receptor 3 (TLR3) is a pattern recognition receptor that senses exogenous (viral) as well as endogenous (mammalian) double-stranded RNA in endosomes. On activation, TLR3 initiates a signal transduction pathway that culminates with the secretion of pro-inflammatory cytokines including type I interferon (IFN). The latter is essential not only for innate immune responses to infection but also for the initiation of antigen-specific immunity against viruses and malignant cells. These aspects of TLR3 biology have supported the development of various agonists for use as stand-alone agents or combined with other therapeutic modalities in cancer patients. Here, we review recent preclinical and clinical advances in the development of TLR3 agonists for oncological disorders.
Abbreviations
cDC, conventional dendritic cell; CMT, cytokine modulating treatment; CRC, colorectal carcinoma; CTL, cytotoxic T lymphocyte; DC, dendritic cell; dsRNA, double-stranded RNA; FLT3LG, fms-related receptor tyrosine kinase 3 ligand; HNSCC, head and neck squamous cell carcinoma; IFN, interferon; IL, interleukin; ISV, in situ vaccine; MUC1, mucin 1, cell surface associated; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; polyA:U, polyadenylic:polyuridylic acid; polyI:C, polyriboinosinic:polyribocytidylic acid; TLR, Toll-like receptor
Acknowledgments
LG is supported by a Breakthrough Level 2 grant from the US Department of Defense (DoD), Breast Cancer Research Program (BRCP) (#BC180476P1), by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C), by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a startup grant from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by industrial collaborations with Lytix (Oslo, Norway) and Phosplatin (New York, US), and by donations from Phosplatin (New York, US), the Luke Heller TECPR2 Foundation (Boston, US) and Sotio a.s. (Prague, Czech Republic). GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Le Cancer du Sein, Parlons-en!”; Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology (ANR-18- IDEX-0001); the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM).
References
- 1. Leulier F, Lemaitre B. Toll-like receptors–taking an evolutionary approach. Nat Rev Genet. 2008;9(3):165–13. doi:10.1038/nrg2303. [] [[PubMed][Google Scholar]
- 2. Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE, Aderem A The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci U S A. 2005;102(27):9577–9582. doi:10.1073/pnas.0502272102. ] [[Google Scholar]
- 3. Brennan JJ, Gilmore TD Evolutionary origins of toll-like receptor signaling. Mol Biol Evol. 2018;35(7):1576–1587. doi:10.1093/molbev/msy050. [] [[PubMed][Google Scholar]
- 4. Wang PH, He JG Nucleic acid sensing in invertebrate antiviral immunity. Int Rev Cell Mol Biol. 2019;345:287–360. [[PubMed][Google Scholar]
- 5. Kawasaki T, Kawai T Toll-like receptor signaling pathways. Front Immunol. 2014;5:461. doi:10.3389/fimmu.2014.00461. ] [[Google Scholar]
- 6. Kumar H, Kawai T, Akira S Toll-like receptors and innate immunity. Biochem Biophys Res Commun. 2009;388(4):621–625. doi:10.1016/j.bbrc.2009.08.062. [] [[PubMed][Google Scholar]
- 7. Ramadan A, Land WG, Paczesny S Editorial: danger Signals Triggering Immune Response and Inflammation. Front Immunol. 2017;8:979. doi:10.3389/fimmu.2017.00979. ] [[Google Scholar]
- 8. Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, Breckpot K, Brough D, Chaurio R, Cirone M, et al Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol. 2015;6:588. doi:10.3389/fimmu.2015.00588. ] [[Google Scholar]
- 9. Gong T, Liu L, Jiang W, Zhou R DAMP-sensing receptors in sterile inflammation and inflammatory diseases. Nat Rev Immunol. 2020;20(2):95–112. doi:10.1038/s41577-019-0215-7. [] [[PubMed][Google Scholar]
- 10. Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12(12):860–875. doi:10.1038/nrc3380. [] [[PubMed][Google Scholar]
- 11. Krysko O, Love Aaes T, Bachert C, Vandenabeele P, Krysko DV Many faces of DAMPs in cancer therapy. Cell Death Dis. 2013;4(5):e631. doi:10.1038/cddis.2013.156. ] [[Google Scholar]
- 12. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–983. doi:10.1016/S0092-8674(00)80172-5. [] [[PubMed][Google Scholar]
- 13. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–397. doi:10.1038/41131. [] [[PubMed][Google Scholar]
- 14. Valanne S, Wang JH, Ramet M The Drosophila toll signaling pathway. J Immunol. 2011;186(2):649–656. doi:10.4049/jimmunol.1002302. [] [[PubMed][Google Scholar]
- 15. Barreiro LB, Ben-Ali M, Quach H, Laval G, Patin E, Pickrell JK, Bouchier C, Tichit M, Neyrolles O, Gicquel B, et al Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet. 2009;5(7):e1000562. doi:10.1371/journal.pgen.1000562. ] [[Google Scholar]
- 16. Minton K. Regulation of endosomal TLRs. Nat Rev Immunol. 2019;19(11):660–661. doi:10.1038/s41577-019-0229-1. [] [[PubMed]
- 17. Chung H, Calis JJA, Wu X, Sun T, Yu Y, Sarbanes SL, Dao Thi VL, Shilvock AR, Hoffmann -H-H, Rosenberg BR, et al Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell. 2018;172(4):811–24 e14. doi:10.1016/j.cell.2017.12.038. ] [[Google Scholar]
- 18. Schlee M, Hartmann G Discriminating self from non-self in nucleic acid sensing. Nat Rev Immunol. 2016;16(9):566–580. doi:10.1038/nri.2016.78. ] [[Google Scholar]
- 19. Vanpouille-Box C, Hoffmann JA, Galluzzi L Pharmacological modulation of nucleic acid sensors - therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2019;18:845–867. [[PubMed][Google Scholar]
- 20. Matz KM, Guzman RM, Goodman AG The role of nucleic acid sensing in controlling microbial and autoimmune disorders. Int Rev Cell Mol Biol. 2019;345:35–136. [Google Scholar]
- 21. Sprooten J, Agostinis P, Garg AD Type I interferons and dendritic cells in cancer immunotherapy. Int Rev Cell Mol Biol. 2019;348:217–262. [[PubMed][Google Scholar]
- 22. Blasius AL, Beutler B Intracellular toll-like receptors. Immunity. 2010;32(3):305–315. doi:10.1016/j.immuni.2010.03.012. [] [[PubMed][Google Scholar]
- 23. Beutler BA. TLRs and innate immunity. Blood. 2009;113(7):1399–1407. doi:10.1182/blood-2008-07-019307. ] [
- 24. Vercammen E, Staal J, Beyaert R Sensing of viral infection and activation of innate immunity by toll-like receptor 3. Clin Microbiol Rev. 2008;21(1):13–25. doi:10.1128/CMR.00022-07. ] [[Google Scholar]
- 25. Crouse J, Kalinke U, Oxenius A Regulation of antiviral T cell responses by type I interferons. Nat Rev Immunol. 2015;15(4):231–242. doi:10.1038/nri3806. [] [[PubMed][Google Scholar]
- 26. Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G Type I interferons in anticancer immunity. Nat Rev Immunol. 2015;15(7):405–414. doi:10.1038/nri3845. [] [[PubMed][Google Scholar]
- 27. Yu M, Levine SJ Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: key modulators of innate immune responses to double-stranded RNA viruses. Cytokine Growth Factor Rev. 2011;22(2):63–72. doi:10.1016/j.cytogfr.2011.02.001. ] [[Google Scholar]
- 28. Gay NJ, Gangloff M, Weber AN Toll-like receptors as molecular switches. Nat Rev Immunol. 2006;6(9):693–698. doi:10.1038/nri1916. [] [[PubMed][Google Scholar]
- 29. Iwakiri D, Zhou L, Samanta M, Matsumoto M, Ebihara T, Seya T, Imai S, Fujieda M, Kawa K, Takada K, et al Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3. J Exp Med. 2009;206(10):2091–2099. doi:10.1084/jem.20081761. ] [[Google Scholar]
- 30. Itoh K, Watanabe A, Funami K, Seya T, Matsumoto M The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-beta production. J Immunol. 2008;181(8):5522–5529. doi:10.4049/jimmunol.181.8.5522. [] [[PubMed][Google Scholar]
- 31. Watanabe A, Tatematsu M, Saeki K, Shibata S, Shime H, Yoshimura A, Obuse C, Seya T, Matsumoto M Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation. J Biol Chem. 2011;286(12):10702–10711. doi:10.1074/jbc.M110.185793. ] [[Google Scholar]
- 32. Salio M, Cerundolo V Viral immunity: cross-priming with the help of TLR3. Curr Biol. 2005;15:R336–9. [[PubMed][Google Scholar]
- 33. Wang W, Wang WH, Azadzoi KM, Su N, Dai P, Sun J, Wang Q, Liang P, Zhang W, Lei X, et al Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis. Sci Rep. 2016;6(1):22550. doi:10.1038/srep22550. ] [[Google Scholar]
- 34. Galluzzi L, Green DR Autophagy-independent functions of the autophagy machinery. Cell. 2019;177(7):1682–1699. doi:10.1016/j.cell.2019.05.026. ] [[Google Scholar]
- 35. Hase K, Contu VR, Kabuta C, Sakai R, Takahashi M, Kataoka N, Hakuno F, Takahashi S-I, Fujiwara Y, Wada K, et al Cytosolic domain of SIDT2 carries an arginine-rich motif that binds to RNA/DNA and is important for the direct transport of nucleic acids into lysosomes. Autophagy. pp.1–15. 2020. doi:10.1080/15548627.2020.1712109 [] [[PubMed][Google Scholar]
- 36. Soreng K, Neufeld TP, Simonsen A Membrane trafficking in autophagy. Int Rev Cell Mol Biol. 2018;336:1–92. [[PubMed][Google Scholar]
- 37. Singh D, Qi R, Jordan JL, San Mateo L, Kao CC The human antimicrobial peptide LL-37, but not the mouse ortholog, mCRAMP, can stimulate signaling by poly(I:C) through a FPRL1-dependent pathway. J Biol Chem. 2013;288(12):8258–8268. doi:10.1074/jbc.M112.440883. ] [[Google Scholar]
- 38. Takahashi T, Kulkarni NN, Lee EY, Zhang LJ, Wong GCL, Gallo RL Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors. Sci Rep. 2018;8(1):4032. doi:10.1038/s41598-018-22409-3. ] [[Google Scholar]
- 39. Kawai T, Akira S TLR signaling. Cell Death Differ. 2006;13(5):816–825. doi:10.1038/sj.cdd.4401850. [] [[PubMed][Google Scholar]
- 40. O’Neill LA, Bowie AG The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7(5):353–364. doi:10.1038/nri2079. [] [[PubMed][Google Scholar]
- 41. Bakshi S, Taylor J, Strickson S, McCartney T, Cohen P Identification of TBK1 complexes required for the phosphorylation of IRF3 and the production of interferon beta. Biochem J. 2017;474(7):1163–1174. doi:10.1042/BCJ20160992. ] [[Google Scholar]
- 42. Doyle S, Vaidya S, O’Connell R, Dadgostar H, Dempsey P, Wu T, Rao G, Sun R, Haberland ME, Modlin RL, et al IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity. 2002;17(3):251–263. doi:10.1016/S1074-7613(02)00390-4. [] [[PubMed][Google Scholar]
- 43. Ning S, Pagano JS, Barber GN IRF7: activation, regulation, modification and function. Genes Immun. 2011;12(6):399–414. doi:10.1038/gene.2011.21. ] [[Google Scholar]
- 44. Galluzzi L, Yamazaki T, Kroemer G Linking cellular stress responses to systemic homeostasis. Nat Rev Mol Cell Biol. 2018;19(11):731–745. doi:10.1038/s41580-018-0068-0. [] [[PubMed][Google Scholar]
- 45. Taniguchi K, Karin M NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18:309–324. [[PubMed][Google Scholar]
- 46. Zhong Z, Sanchez-Lopez E, Karin MAutophagy, inflammation, and immunity: a troika governing cancer and its treatment. Cell. 2016;166(2):288–298. doi:10.1016/j.cell.2016.05.051. ] [[Google Scholar]
- 47. Sen GC, Sarkar SN Transcriptional signaling by double-stranded RNA: role of TLR3. Cytokine Growth Factor Rev. 2005;16(1):1–14. doi:10.1016/j.cytogfr.2005.01.006. [] [[PubMed][Google Scholar]
- 48. Gosu V, Basith S, Kwon OP, Choi S Therapeutic applications of nucleic acids and their analogues in Toll-like receptor signaling. Molecules. 2012;17(11):13503–13529. doi:10.3390/molecules171113503. ] [[Google Scholar]
- 49. Sarkar SN, Smith HL, Rowe TM, Sen GC Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine residues in its cytoplasmic domain. J Biol Chem. 2003;278(7):4393–4396. doi:10.1074/jbc.C200655200. [] [[PubMed][Google Scholar]
- 50. Wen AY, Sakamoto KM, Miller LS The role of the transcription factor CREB in immune function. J Immunol. 2010;185(11):6413–6419. doi:10.4049/jimmunol.1001829. ] [[Google Scholar]
- 51. Peroval MY, Boyd AC, Young JR, Smith AL A critical role for MAPK signalling pathways in the transcriptional regulation of toll like receptors. PLoS One. 2013;8(2):e51243. doi:10.1371/journal.pone.0051243. ] [[Google Scholar]
- 52. Campos PC, Gomes MT, Guimaraes ES, Guimaraes G, Oliveira SC TLR7 and TLR3 sense brucella abortus RNA to induce proinflammatory cytokine production but they are dispensable for host control of infection. Front Immunol. 2017;8:28. doi:10.3389/fimmu.2017.00028. ] [[Google Scholar]
- 53. Ryu JH, Park M, Kim BK, Ryu KH, Woo SY Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation. Cytokine. 2015;73(2):225–235. doi:10.1016/j.cyto.2015.02.028. [] [[PubMed][Google Scholar]
- 54. Tan LSY, Wong B, Gangodu NR, Lee AZE, Kian Fong Liou A, KS L, Li H, Yann Lim M, Salazar AM, Lim CM, et al Enhancing the immune stimulatory effects of cetuximab therapy through TLR3 signalling in Epstein-Barr virus (EBV) positive nasopharyngeal carcinoma. Oncoimmunology. 2018;7(11):e1500109. doi:10.1080/2162402X.2018.1500109. ] [[Google Scholar]
- 55. Lai Y, Gallo RL Toll-like receptors in skin infections and inflammatory diseases. Infect Disord Drug Targets. 2008;8(3):144–155. doi:10.2174/1871526510808030144. ] [[Google Scholar]
- 56. Uematsu S, Akira S Toll-like receptors and Type I interferons. J Biol Chem. 2007;282(21):15319–15323. doi:10.1074/jbc.R700009200. [] [[PubMed][Google Scholar]
- 57. Vacchelli E, Sistigu A, Yamazaki T, Vitale I, Zitvogel L, Kroemer G, Starmann J, Tjwa M, Plate KH, Sültmann H Autocrine signaling of type 1 interferons in successful anticancer chemotherapy. Oncoimmunology. 2015;4(6):e988042. doi:10.1080/2162402X.2015.1008371. ] [[Google Scholar]
- 58. Sarkar SN, Peters KL, Elco CP, Sakamoto S, Pal S, Sen GC Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat Struct Mol Biol. 2004;11(11):1060–1067. doi:10.1038/nsmb847. [] [[PubMed][Google Scholar]
- 59. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301(5633):640–643. doi:10.1126/science.1087262. [] [[PubMed][Google Scholar]
- 60. Holtorf A, Conrad A, Holzmann B, Janssen KP Cell-type specific MyD88 signaling is required for intestinal tumor initiation and progression to malignancy. Oncoimmunology. 2018;7:e1466770. doi:10.1080/2162402X.2018.1466770. ] [[Google Scholar]
- 61. Gosu V, Son S, Shin D, Song KD Insights into the dynamic nature of the dsRNA-bound TLR3 complex. Sci Rep. 2019;9(1):3652. doi:10.1038/s41598-019-39984-8. ] [[Google Scholar]
- 62. Wang Y, Zhang S, Li H, Wang H, Zhang T, Hutchinson MR, Yin H, Wang X Small-molecule modulators of toll-like receptors. Acc Chem Res. 2020. doi:10.1021/acs.accounts.9b00631. [] [[PubMed][Google Scholar]
- 63. Vacchelli E, Enot DP, Pietrocola F, Zitvogel L, Kroemer G Impact of pattern recognition receptors on the prognosis of breast cancer patients undergoing adjuvant chemotherapy. Cancer Res. 2016;76(11):3122–3126. doi:10.1158/0008-5472.CAN-16-0294. [] [[PubMed][Google Scholar]
- 64. Vacchelli E, Ma Y, Baracco EE, Sistigu A, Enot DP, Pietrocola F, Yang H, Adjemian S, Chaba K, Semeraro M, et al Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1. Science. 2015;350(6263):972–978. doi:10.1126/science.aad0779. [] [[PubMed][Google Scholar]
- 65. Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly. J Virol. 2008;82(15):7613–7623. doi:10.1128/JVI.00618-08. ] [[Google Scholar]
- 66. Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C, et al Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014;20(11):1301–1309. doi:10.1038/nm.3708. [] [[PubMed][Google Scholar]
- 67. Yeyeodu ST, Kidd LR, Oprea-Ilies GM, Burns BG, Vancleave TT, Shim JY, et al IRAK4 and TLR3 sequence variants may alter breast cancer risk among African-Aamerican women. Front Immunol. 2013;4:338. doi:10.3389/fimmu.2013.00338. ] [[Google Scholar]
- 68. Hasimu A, Ge L, Li QZ, Zhang RP, Guo X Expressions of Toll-like receptors 3, 4, 7, and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women. Chin J Cancer. 2011;30(5):344–350. doi:10.5732/cjc.010.10456. ] [[Google Scholar]
- 69. Zeljic K, Supic G, Jovic N, Kozomara R, Brankovic-Magic M, Obrenovic M, Magic Z Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival. Oral Dis. 2014;20(4):416–424. doi:10.1111/odi.12144. [] [[PubMed][Google Scholar]
- 70. Li G, Zheng Z Toll-like receptor 3 genetic variants and susceptibility to hepatocellular carcinoma and HBV-related hepatocellular carcinoma. Tumour Biol. 2013;34(3):1589–1594. doi:10.1007/s13277-013-0689-z. [] [[PubMed][Google Scholar]
- 71. Slattery ML, Herrick JS, Bondurant KL, Wolff RK Toll-like receptor genes and their association with colon and rectal cancer development and prognosis. Int J Cancer. 2012;130(12):2974–2980. doi:10.1002/ijc.26314. ] [[Google Scholar]
- 72. Castro FA, Forsti A, Buch S, Kalthoff H, Krauss C, Bauer M, Egberts J, Schniewind B, Broering DC, Schreiber S, et al TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer. Eur J Cancer. 2011;47(8):1203–1210. doi:10.1016/j.ejca.2010.12.011. [] [[PubMed][Google Scholar]
- 73. Dai J, Hu Z, Dong J, Xu L, Pan S, Jiang Y, Jin G, Chen Y, Shen H Host immune gene polymorphisms were associated with the prognosis of non-small-cell lung cancer in Chinese. Int J Cancer. 2012;130(3):671–676. doi:10.1002/ijc.26067. [] [[PubMed][Google Scholar]
- 74. Chew V, Tow C, Huang C, Bard-Chapeau E, Copeland NG, Jenkins NA, Weber A, Lim KH, Toh HC, Heikenwalder M, et al Toll-like receptor 3 expressing tumor parenchyma and infiltrating natural killer cells in hepatocellular carcinoma patients. J Natl Cancer Inst. 2012;104(23):1796–1807. doi:10.1093/jnci/djs436. ] [[Google Scholar]
- 75. Yuan MM, Xu YY, Chen L, Li XY, Qin J, Shen Y TLR3 expression correlates with apoptosis, proliferation and angiogenesis in hepatocellular carcinoma and predicts prognosis. BMC Cancer. 2015;15:245. [Google Scholar]
- 76. Hsu WM, Huang CC, Wu PY, Lee H, Huang MC, Tai MH, Chuang J-H Toll-like receptor 3 expression inhibits cell invasion and migration and predicts a favorable prognosis in neuroblastoma. Cancer Lett. 2013;336(2):338–346. doi:10.1016/j.canlet.2013.03.024. [] [[PubMed][Google Scholar]
- 77. Salaun B, Zitvogel L, Asselin-Paturel C, Morel Y, Chemin K, Dubois C, Massacrier C, Conforti R, Chenard MP, Sabourin J-C, et al TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer. Cancer Res. 2011;71(5):1607–1614. doi:10.1158/0008-5472.CAN-10-3490. [] [[PubMed][Google Scholar]
- 78. Deutsch E, Chargari C, Galluzzi L, Kroemer G Optimising efficacy and reducing toxicity of anticancer radioimmunotherapy. Lancet Oncol. 2019;20(8):e452–e63. doi:10.1016/S1470-2045(19)30171-8. [] [[PubMed][Google Scholar]
- 79. Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97–111. doi:10.1038/nri.2016.107. [] [[PubMed][Google Scholar]
- 80. Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Martinez AB Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020;88(1):e000337. [Google Scholar]
- 81. Garg AD, Agostinis P Cell death and immunity in cancer: from danger signals to mimicry of pathogen defense responses. Immunol Rev. 2017;280(1):126–148. doi:10.1111/imr.12574. [] [[PubMed][Google Scholar]
- 82. Vacchelli E, Ma Y, Baracco EE, Zitvogel L, Kroemer G Yet another pattern recognition receptor involved in the chemotherapy-induced anticancer immune response: formyl peptide receptor-1. Oncoimmunology. 2016;5(5):e1118600. doi:10.1080/2162402X.2015.1118600. ] [[Google Scholar]
- 83. Galluzzi L, Chan TA, Kroemer G, Wolchok JD, Lopez-Soto A The hallmarks of successful anticancer immunotherapy. Sci Transl Med. 2018;10(459):eaat7807. [[PubMed][Google Scholar]
- 84. Medler T, Patel JM, Alice A, Baird JR, Hu HM, Gough MJ Activating the nucleic acid-sensing machinery for anticancer immunity. Int Rev Cell Mol Biol. 2019;344:173–214. [Google Scholar]
- 85. Pastor F, Berraondo P, Etxeberria I, Frederick J, Sahin U, Gilboa E, Melero I An RNA toolbox for cancer immunotherapy. Nat Rev Drug Discov. 2018;17(10):751–767. doi:10.1038/nrd.2018.132. [] [[PubMed][Google Scholar]
- 86. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020;20(1):7–24. doi:10.1038/s41577-019-0210-z. [] [[PubMed][Google Scholar]
- 87. Hennessy EJ, Parker AE, O’Neill LA Targeting Toll-like receptors: emerging therapeutics?Nat Rev Drug Discov. 2010;9(4):293–307. doi:10.1038/nrd3203. [] [[PubMed][Google Scholar]
- 88. Vacchelli E, Galluzzi L, Eggermont A, Fridman WH, Galon J, Sautes-Fridman C Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012;1:894–907. [Google Scholar]
- 89. Bezu L, Kepp O, Cerrato G, Pol J, Fucikova J, Spisek R, Zitvogel L, Kroemer G, Galluzzi L Trial watch: peptide-based vaccines in anticancer therapy. Oncoimmunology. 2018;7(12):e1511506. doi:10.1080/2162402X.2018.1511506. ] [[Google Scholar]
- 90. Smith M, Garcia-Martinez E, Pitter MR, Fucikova J, Spisek R, Zitvogel L, Kroemer G, Galluzzi L Trial Watch: toll-like receptor agonists in cancer immunotherapy. Oncoimmunology. 2018;7(12):e1526250. doi:10.1080/2162402X.2018.1526250. ] [[Google Scholar]
- 91. Maisonneuve C, Bertholet S, Philpott DJ, De Gregorio E Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants. Proc Natl Acad Sci U S A. 2014;111(34):12294–12299. doi:10.1073/pnas.1400478111. ] [[Google Scholar]
- 92. Marshall-Clarke S, Downes JE, Haga IR, Bowie AG, Borrow P, Pennock JL, Grencis RK, Rothwell P Polyinosinic acid is a ligand for toll-like receptor 3. J Biol Chem. 2007;282(34):24759–24766. doi:10.1074/jbc.M700188200. [] [[PubMed][Google Scholar]
- 93. Sugiyama T, Hoshino K, Saito M, Yano T, Sasaki I, Yamazaki C, Akira S, Kaisho T Immunoadjuvant effects of polyadenylic: polyuridylicacids through TLR3 and TLR7. Int Immunol. 2008;20(1):1–9. doi:10.1093/intimm/dxm112. [] [[PubMed][Google Scholar]
- 94. Salazar AM, Erlich RB, Mark A, Bhardwaj N, Herberman RB Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial. Cancer Immunol Res. 2014;2(8):720–724. doi:10.1158/2326-6066.CIR-14-0024. [] [[PubMed][Google Scholar]
- 95. Brodsky I, Strayer DR, Krueger LJ, Carter WA Clinical studies with ampligen (mismatched double-stranded RNA). J Biol Response Mod. 1985;4:669–675. [[PubMed][Google Scholar]
- 96. Navabi H, Jasani B, Reece A, Clayton A, Tabi Z, Donninger C, Mason M, Adams M A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro. Vaccine. 2009;27(1):107–115. doi:10.1016/j.vaccine.2008.10.024. [] [[PubMed][Google Scholar]
- 97. Berk E, Kalinski P Lymphocyte-polarized DC1s: effective inducers of tumor-specific CTLs. Oncoimmunology. 2012;1(8):1443–1444. doi:10.4161/onci.21295. ] [[Google Scholar]
- 98. Bianchi F, Pretto S, Tagliabue E, Balsari A, Sfondrini L Exploiting poly(I:C) to induce cancer cell apoptosis. Cancer Biol Ther. 2017;18(10):747–756. doi:10.1080/15384047.2017.1373220. ] [[Google Scholar]
- 99. Conforti R, Ma Y, Morel Y, Paturel C, Terme M, Viaud S, Ryffel B, Ferrantini M, Uppaluri R, Schreiber R, et al Opposing effects of toll-like receptor (TLR3) signaling in tumors can be therapeutically uncoupled to optimize the anticancer efficacy of TLR3 ligands. Cancer Res. 2010;70(2):490–500. doi:10.1158/0008-5472.CAN-09-1890. [] [[PubMed][Google Scholar]
- 100. Nicodemus CF, Berek JS TLR3 agonists as immunotherapeutic agents. Immunotherapy. 2010;2(2):137–140. doi:10.2217/imt.10.8. [] [[PubMed][Google Scholar]
- 101. Sharma S, Zhu L, Davoodi M, Harris-White M, Lee JM, St John M, Salgia R, Dubinett S TLR3 agonists and proinflammatory antitumor activities. Expert Opin Ther Targets. 2013;17(5):481–483. doi:10.1517/14728222.2013.781585. ] [[Google Scholar]
- 102. Adams S. Toll-like receptor agonists in cancer therapy. Immunotherapy. 2009;1(6):949–964. doi:10.2217/imt.09.70. ] [
- 103. Aranda F, Vacchelli E, Obrist F, Eggermont A, Galon J, Sautes-Fridman C, Cremer I, Henrik Ter Meulen J, Zitvogel L, Kroemer G, et al Trial Watch: toll-like receptor agonists in oncological indications. Oncoimmunology. 2014;3(6):e29179. doi:10.4161/onci.29179. ] [[Google Scholar]
- 104. Devaud C, John LB, Westwood JA, Darcy PK, Kershaw MH Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy. Oncoimmunology. 2013;2(8):e25961. doi:10.4161/onci.25961. ] [[Google Scholar]
- 105. Lu L, Barbi J, Pan F The regulation of immune tolerance by FOXP3. Nat Rev Immunol. 2017;17(11):703–717. doi:10.1038/nri.2017.75. ] [[Google Scholar]
- 106. Togashi Y, Shitara K, Nishikawa H Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16(6):356–371. doi:10.1038/s41571-019-0175-7. [] [[PubMed][Google Scholar]
- 107. O’Donnell JS, Teng MWL, Smyth MJ Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151–167. doi:10.1038/s41571-018-0142-8. [] [[PubMed][Google Scholar]
- 108. Rodriguez-Ruiz ME, Vitale I, Harrington KJ, Melero I, Galluzzi L Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat Immunol. 2020;21(2):120–134. doi:10.1038/s41590-019-0561-4. [] [[PubMed][Google Scholar]
- 109. Field AK, Tytell AA, Lampson GP, Hilleman MR Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes. Proc Natl Acad Sci U S A. 1967;58(3):1004–1010. doi:10.1073/pnas.58.3.1004. ] [[Google Scholar]
- 110. Yarchoan M, Johnson BA 3rd, Lutz ER, Laheru DA, Jaffee EM Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17(4):209–222. doi:10.1038/nrc.2016.154. ] [[Google Scholar]
- 111. Verdijk RM, Mutis T, Esendam B, Kamp J, Melief CJ, Brand A, Goulmy E Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol. 1999;163:57–61. [[PubMed][Google Scholar]
- 112. Jelinek I, Leonard JN, Price GE, Brown KN, Meyer-Manlapat A, Goldsmith PK, Wang Y, Venzon D, Epstein SL, Segal DM, et al TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J Immunol. 2011;186(4):2422–2429. doi:10.4049/jimmunol.1002845. ] [[Google Scholar]
- 113. Miller JC, Brown BD, Shay T, Gautier EL, Jojic V, Cohain A, Pandey G, Leboeuf M, Elpek KG, Helft J, et al Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol. 2012;13(9):888–899. doi:10.1038/ni.2370. ] [[Google Scholar]
- 114. Roselli E, Araya P, Nunez NG, Gatti G, Graziano F, Sedlik C, Benaroch P, Piaggio E, Maccioni M TLR3 activation of intratumoral CD103+ dendritic cells modifies the tumor infiltrate conferring anti-tumor immunity. Front Immunol. 2019;10:503. doi:10.3389/fimmu.2019.00503. ] [[Google Scholar]
- 115. Bachem A, Guttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, Salama A, Movassaghi K, Opitz C, Mages HW, et al Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J Exp Med. 2010;207(6):1273–1281. doi:10.1084/jem.20100348. ] [[Google Scholar]
- 116. Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X, Angel CE, Chen CJJ, Dunbar PR, Wadley RB, Jeet V, et al Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med. 2010;207(6):1247–1260. doi:10.1084/jem.20092140. ] [[Google Scholar]
- 117. Balan S, Saxena M, Bhardwaj N Dendritic cell subsets and locations. Int Rev Cell Mol Biol. 2019;348:1–68. [[PubMed][Google Scholar]
- 118. Eisenbarth SC. Dendritic cell subsets in T cell programming: location dictates function. Nat Rev Immunol. 2019;19(2):89–103. doi:10.1038/s41577-018-0088-1. [] [[PubMed]
- 119. Lee YS, Radford KJ The role of dendritic cells in cancer. Int Rev Cell Mol Biol. 2019;348:123–178. [[PubMed][Google Scholar]
- 120. Spranger S, Dai D, Horton B, Gajewski TF Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 2017;31(5):711–23 e4. doi:10.1016/j.ccell.2017.04.003. ] [[Google Scholar]
- 121. Corrales L, Matson V, Flood B, Spranger S, Gajewski TF Innate immune signaling and regulation in cancer immunotherapy. Cell Res. 2017;27(1):96–108. doi:10.1038/cr.2016.149. ] [[Google Scholar]
- 122. Kotsias F, Cebrian I, Alloatti A Antigen processing and presentation. Int Rev Cell Mol Biol. 2019;348:69–121. [[PubMed][Google Scholar]
- 123. Kline DE, MacNabb BW, Chen X, Chan WC, Fosco D, Kline J CD8α+dendritic cells dictate leukemia-specific CD8+T cell fates. J Immunol. 2018;201(12):3759–3769. doi:10.4049/jimmunol.1801184. ] [[Google Scholar]
- 124. Guinn ZP, Petro TM IFN-gamma synergism with poly I:C reduces growth of murine and human cancer cells with simultaneous changes in cell cycle and immune checkpoint proteins. Cancer Lett. 2018;438:1–9. doi:10.1016/j.canlet.2018.09.003. [] [[PubMed][Google Scholar]
- 125. Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S, Casanova-Acebes M, Khudoynazarova M, Agudo J, Tung N, et al Expansion and activation of CD103 + dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity. 2016;44(4):924–938. doi:10.1016/j.immuni.2016.03.012. ] [[Google Scholar]
- 126. Di S, Zhou M, Pan Z, Sun R, Chen M, Jiang H Combined adjuvant of poly I:C improves antitumor effects of CAR-T Cells. Front Oncol. 2019;9:241. doi:10.3389/fonc.2019.00241. ] [[Google Scholar]
- 127. Zhao J, Xue Y, Pan Y, Yao A, Wang G, Li D, Wang T, Zhao S, Hou Y Toll-like receptor 3 agonist poly I:C reinforces the potency of cytotoxic chemotherapy via the TLR3-UNC93B1-IFN-beta signaling axis in paclitaxel-resistant colon cancer. J Cell Physiol. 2019;234(5):7051–7061. doi:10.1002/jcp.27459. [] [[PubMed][Google Scholar]
- 128. Zitvogel L, Kroemer G CD103+ dendritic cells producing interleukin-12 in anticancer immunosurveillance. Cancer Cell. 2014;26(5):591–593. doi:10.1016/j.ccell.2014.10.008. [] [[PubMed][Google Scholar]
- 129. Whilding LM, Maher J ErbB-targeted CAR T-cell immunotherapy of cancer. Immunotherapy. 2015;7(3):229–241. doi:10.2217/imt.14.120. [] [[PubMed][Google Scholar]
- 130. Alqahtani FY, Aleanizy FS, El Tahir E, Alkahtani HM, AlQuadeib BT Paclitaxel. Profiles Drug Subst Excip Relat Methodol. 2019;44:205–238. [[PubMed][Google Scholar]
- 131. Vanpouille-Box C, Demaria S, Formenti SC, Galluzzi L Cytosolic DNA sensing in organismal tumor control. Cancer Cell. 2018;34(3):361–378. doi:10.1016/j.ccell.2018.05.013. [] [[PubMed][Google Scholar]
- 132. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ. 2018;25:486–541. [Google Scholar]
- 133. Kaiser WJ, Offermann MK Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J Immunol. 2005;174(8):4942–4952. doi:10.4049/jimmunol.174.8.4942. [] [[PubMed][Google Scholar]
- 134. Conrad M, Angeli JP, Vandenabeele P, Stockwell BR Regulated necrosis: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2016;15(5):348–366. doi:10.1038/nrd.2015.6. ] [[Google Scholar]
- 135. Kaiser WJ, Sridharan H, Huang C, Mandal P, Upton JW, Gough PJ, Sehon CA, Marquis RW, Bertin J, Mocarski ES, et al Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J Biol Chem. 2013;288(43):31268–31279. doi:10.1074/jbc.M113.462341. ] [[Google Scholar]
- 136. Weinlich R, Oberst A, Beere HM, Green DR Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol. 2017;18(2):127–136. doi:10.1038/nrm.2016.149. [] [[PubMed][Google Scholar]
- 137. Galluzzi L, Kepp O, Chan FK, Kroemer G Necroptosis: mechanisms and relevance to disease. Annu Rev Pathol. 2017;12(1):103–130. doi:10.1146/annurev-pathol-052016-100247. ] [[Google Scholar]
- 138. Takemura R, Takaki H, Okada S, Shime H, Akazawa T, Oshiumi H, Matsumoto M, Teshima T, Seya T PolyI:C-Induced, TLR3/RIP3-dependent necroptosis backs up immune effector-mediated tumor elimination in vivo. Cancer Immunol Res. 2015;3(8):902–914. doi:10.1158/2326-6066.CIR-14-0219. [] [[PubMed][Google Scholar]
- 139. Aznar MA, Planelles L, Perez-Olivares M, Molina C, Garasa S, Etxeberria I, Perez G, Rodriguez I, Bolaños E, Lopez-Casas P, et al Immunotherapeutic effects of intratumoral nanoplexed poly I:C. J Immunother Cancer. 2019;7(1):116. doi:10.1186/s40425-019-0568-2. ] [[Google Scholar]
- 140. Palchetti S, Starace D, De Cesaris P, Filippini A, Ziparo E, Riccioli A Transfected poly(I:C) activates different dsRNA receptors, leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells. J Biol Chem. 2015;290(9):5470–5483. doi:10.1074/jbc.M114.601625. ] [[Google Scholar]
- 141. Song H, Huang P, Niu J, Shi G, Zhang C, Kong D, Wang W Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma. Biomaterials. 2018;159:119–129. doi:10.1016/j.biomaterials.2018.01.004. [] [[PubMed][Google Scholar]
- 142. Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Delage G, Contesso G, Viguier J Adjuvant treatment with polyadenylic-polyuridylic acid (Polya.Polyu) in operable breast cancer. Lancet. 1980;2(8187):161–164. doi:10.1016/S0140-6736(80)90057-4. [] [[PubMed][Google Scholar]
- 143. Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J Adjuvant treatment with polyadenylic-polyuridylic acid in operable breast cancer: updated results of a randomised trial. Br Med J (Clin Res Ed). 1984;288(6417):589–592. doi:10.1136/bmj.288.6417.589. ] [[Google Scholar]
- 144. Ducret JP, Caille P, Sancho Garnier H, Amiel JL, Michelson M, Hovanessian AG, Youn JK, Lacour F A phase I clinical tolerance study of polyadenylic-polyuridylic acid in cancer patients. J Biol Response Mod. 1985;4:129–133. [[PubMed][Google Scholar]
- 145. Levine AS, Levy HB Phase I-II trials of poly IC stabilized with poly-L-lysine. Cancer Treat Rep. 1978;62:1907–1912. [[PubMed][Google Scholar]
- 146. Robinson RA, DeVita VT, Levy HB, Baron S, Hubbard SP, Levine AS A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors. J Natl Cancer Inst. 1976;57(3):599–602. doi:10.1093/jnci/57.3.599. [] [[PubMed][Google Scholar]
- 147. Perrot I, Deauvieau F, Massacrier C, Hughes N, Garrone P, Durand I, Demaria O, Viaud N, Gauthier L, Blery M, et al TLR3 and Rig-like receptor on myeloid dendritic cells and Rig-like receptor on human NK cells are both mandatory for production of IFN-gamma in response to double-stranded RNA. J Immunol. 2010;185(4):2080–2088. doi:10.4049/jimmunol.1000532. ] [[Google Scholar]
- 148. Nowacki TM, Kuerten S, Zhang W, Shive CL, Kreher CR, Boehm BO, Lehmann PV, Tary-Lehmann M Granzyme B production distinguishes recently activated CD8(+) memory cells from resting memory cells. Cell Immunol. 2007;247(1):36–48. doi:10.1016/j.cellimm.2007.07.004. ] [[Google Scholar]
- 149. Sharpe AH, Pauken KE The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018;18(3):153–167. doi:10.1038/nri.2017.108. [] [[PubMed][Google Scholar]
- 150. Park SJ, Ye W, Xiao R, Silvin C, Padget M, Hodge JW, Van Waes C, Schmitt NC Cisplatin and oxaliplatin induce similar immunogenic changes in preclinical models of head and neck cancer. Oral Oncol. 2019;95:127–135. doi:10.1016/j.oraloncology.2019.06.016. ] [[Google Scholar]
- 151. Yamazaki T, Buque A, Ames TD, Galluzzi L PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models. Oncoimmunology. 2020;9(1):1721810. doi:10.1080/2162402X.2020.1721810. ] [[Google Scholar]
- 152. Rao S, Gharib K, Han A Cancer Immunosurveillance by T Cells. Int Rev Cell Mol Biol. 2019;342:149–173. [[PubMed][Google Scholar]
- 153. Sharma P, Allison JP Dissecting the mechanisms of immune checkpoint therapy. Nat Rev Immunol. 2020;20(2):75–76. doi:10.1038/s41577-020-0275-8. [] [[PubMed][Google Scholar]
- 154. Jasani B, Navabi H, Adams M Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine. 2009;27(25–26):3401–3404. doi:10.1016/j.vaccine.2009.01.071. [] [[PubMed][Google Scholar]
- 155. Strayer DR, Carter WA, Strauss KI, Brodsky I, Suhadolnik R, Ablashi O, Henry B, Mitchell WM, Bastien S, Peterson D, et al Long term improvements in patients with chronic fatigue syndrome treated with ampligen. J Chronic Fatigue Syndr. 1995;1(1):35–53. doi:10.1300/J092v01n01_04. [[PubMed][Google Scholar]
- 156. Strayer DR, Carter WA, Stouch BC, Stevens SR, Bateman L, Cimoch PJ, Lapp CW, Peterson DL, Mitchell WM A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLoS One. 2012;7(3):e31334. doi:10.1371/journal.pone.0031334. ] [[Google Scholar]
- 157. Killock D. Haematological cancer: resiquimod-a topical CTCL therapy. Nat Rev Clin Oncol. 2015;12(10):563. doi:10.1038/nrclinonc.2015.142. [] [[PubMed]
- 158. Nishii N, Tachinami H, Kondo Y, Xia Y, Kashima Y, Ohno T, Nagai S, Li L, Lau W, Harada H, et al Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy. Oncotarget. 2018;9(17):13301–13312. doi:10.18632/oncotarget.24327. ] [[Google Scholar]
- 159. Gutierrez C, Schiff R HER2: biology, detection, and clinical implications. Arch Pathol Lab Med. 2011;135(1):55–62. doi:10.1043/2010-0454-RAR.1. ] [[Google Scholar]
- 160. Nath S, Mukherjee P MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends Mol Med. 2014;20(6):332–342. doi:10.1016/j.molmed.2014.02.007. ] [[Google Scholar]
- 161. Tomasicchio M, Semple L, Esmail A, Meldau R, Randall P, Pooran A, Davids M, Cairncross L, Anderson D, Downs J, et al An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells. Cancer Immunol Immunother. 2019;68(1):71–83. doi:10.1007/s00262-018-2238-5. ] [[Google Scholar]
- 162. Naumann K, Wehner R, Schwarze A, Petzold C, Schmitz M, Rohayem J Activation of dendritic cells by the novel Toll-like receptor 3 agonist RGC100. Clin Dev Immunol. 2013;2013:283649. doi:10.1155/2013/283649. ] [[Google Scholar]
- 163. Jain A, Barve A, Zhao Z, Jin W, Cheng K Comparison of avidin, neutravidin, and streptavidin as nanocarriers for efficient siRNA delivery. Mol Pharm. 2017;14(5):1517–1527. doi:10.1021/acs.molpharmaceut.6b00933. ] [[Google Scholar]
- 164. Vermette P, Gengenbach T, Divisekera U, Kambouris PA, Griesser HJ, Meagher L Immobilization and surface characterization of NeutrAvidin biotin-binding protein on different hydrogel interlayers. J Colloid Interface Sci. 2003;259(1):13–26. doi:10.1016/S0021-9797(02)00185-6. [] [[PubMed][Google Scholar]
- 165. Schau I, Michen S, Hagstotz A, Janke A, Schackert G, Appelhans D, Temme A Targeted delivery of TLR3 agonist to tumor cells with single chain antibody fragment-conjugated nanoparticles induces type I-interferon response and apoptosis. Sci Rep. 2019;9(1):3299. doi:10.1038/s41598-019-40032-8. ] [[Google Scholar]
- 166. Matsumoto M, Tatematsu M, Nishikawa F, Azuma M, Ishii N, Morii-Sakai A, Shime H, Seya T Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo. Nat Commun. 2015;6(1):6280. doi:10.1038/ncomms7280. [] [[PubMed][Google Scholar]
- 167. Khodarev NN. Intracellular RNA sensing in mammalian cells: role in stress response and cancer therapies. Int Rev Cell Mol Biol. 2019;344:31–89. [[PubMed]
- 168. Rehwinkel J, Gack MU RIG-I-like receptors: their regulation and roles in RNA sensing. Nat Rev Immunol. 2020. doi:10.1038/s41577-020-0288-3. ] [[Google Scholar]
- 169. Matsumoto M, Takeda Y, Seya T Targeting Toll-like receptor 3 in dendritic cells for cancer immunotherapy. Expert Opin Biol Ther. 2020;1–10. doi:10.1080/14712598.2020.1749260. [] [[PubMed][Google Scholar]
- 170. Seya T, Takeda Y, Matsumoto M Tumor vaccines with dsRNA adjuvant ARNAX induces antigen-specific tumor shrinkage without cytokinemia. Oncoimmunology. 2016;5(2):e1043506. doi:10.1080/2162402X.2015.1043506. ] [[Google Scholar]
- 171. Seya T, Takeda Y, Takashima K, Yoshida S, Azuma M, Matsumoto M Adjuvant immunotherapy for cancer: both dendritic cell-priming and check-point inhibitor blockade are required for immunotherapy. Proc Jpn Acad Ser B Phys Biol Sci. 2018;94(3):153–160. doi:10.2183/pjab.94.011. ] [[Google Scholar]
- 172. Takeda Y, Yoshida S, Takashima K, Ishii-Mugikura N, Shime H, Seya T, Matsumoto M Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models. Cancer Sci. 2018;109(7):2119–2129. doi:10.1111/cas.13649. ] [[Google Scholar]
- 173. Bianchi F, Milione M, Casalini P, Centonze G, Le Noci VM, Storti C, Alexiadis S, Truini M, Sozzi G, Pastorino U, et al Toll-like receptor 3 as a new marker to detect high risk early stage non-small-cell lung cancer patients. Sci Rep. 2019;9(1):14288. doi:10.1038/s41598-019-50756-2. ] [[Google Scholar]
- 174. Galluzzi L, Lopez-Soto A, Kumar S, Kroemer G Caspases connect cell-death signaling to organismal homeostasis. Immunity. 2016;44(2):221–231. doi:10.1016/j.immuni.2016.01.020. [] [[PubMed][Google Scholar]
- 175. Man SM, Kanneganti TD Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat Rev Immunol. 2016;16(1):7–21. doi:10.1038/nri.2015.7. ] [[Google Scholar]
- 176. Rodriguez-Ruiz ME, Buque A, Hensler M, Chen J, Bloy N, Petroni G, Sato A, Yamazaki T, Fucikova J, Galluzzi L, et al Apoptotic caspases inhibit abscopal responses to radiation and identify a new prognostic biomarker for breast cancer patients. Oncoimmunology. 2019;8(11):e1655964. doi:10.1080/2162402X.2019.1655964. ] [[Google Scholar]
- 177. Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019;25(5):814–824. doi:10.1038/s41591-019-0410-x. [] [[PubMed][Google Scholar]
- 178. Hassel JC, Jiang H, Bender C, Winkler J, Sevko A, Shevchenko I, Halama N, Dimitrakopoulou-Strauss A, Haefeli WE, Jäger D, et al Tadalafil has biologic activity in human melanoma. Results of a pilot trial with Ta dalafil in patients with metastatic Melanoma (TaMe). Oncoimmunology. 2017;6(9):e1326440. doi:10.1080/2162402X.2017.1326440. ] [[Google Scholar]
- 179. Weed DT, Zilio S, Reis IM, Sargi Z, Abouyared M, Gomez-Fernandez CR, Civantos FJ, Rodriguez CP, Serafini P The reversal of immune exclusion mediated by tadalafil and an anti-tumor vaccine also induces PDL1 upregulation in recurrent head and neck squamous cell carcinoma: interim analysis of a phase I clinical trial. Front Immunol. 2019;10:1206. doi:10.3389/fimmu.2019.01206. ] [[Google Scholar]
- 180. Kyi C, Roudko V, Sabado R, Saenger Y, Loging W, Mandeli J, Thin TH, Lehrer D, Donovan M, Posner M, et al Therapeutic immune modulation against solid cancers with intratumoral poly-ICLC: a pilot trial. Clin Cancer Res. 2018;24(20):4937–4948. doi:10.1158/1078-0432.CCR-17-1866. ] [[Google Scholar]
- 181. Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie W-R, Hildebrand WH, Mardis ER, et al Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015;348(6236):803–808. doi:10.1126/science.aaa3828. ] [[Google Scholar]
- 182. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, et al An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217–221. doi:10.1038/nature22991. ] [[Google Scholar]
- 183. Sahin U, Derhovanessian E, Miller M, BP K, Simon P, Lower M, Bukur V, Tadmor AD, Luxemburger U, Schrörs B, et al Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222–226. doi:10.1038/nature23003. [] [[PubMed][Google Scholar]
- 184. Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, et al Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234–239. doi:10.1038/s41586-018-0792-9. ] [[Google Scholar]
- 185. Rutledge WC, Kong J, Gao J, Gutman DA, Cooper LA, Appin C Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin Cancer Res. 2013;19(18):4951–4960. doi:10.1158/1078-0432.CCR-13-0551. ] [[Google Scholar]
- 186. Johanns TM, Miller CA, Liu CJ, Perrin RJ, Bender D, Kobayashi DK, Campian JL, Chicoine MR, Dacey RG, Huang J, et al Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma. Oncoimmunology. 2019;8(4):e1561106. doi:10.1080/2162402X.2018.1561106. ] [[Google Scholar]
- 187. Ferrara N, Adamis AP Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15(6):385–403. doi:10.1038/nrd.2015.17. [] [[PubMed][Google Scholar]
- 188. Kazazi-Hyseni F, Beijnen JH, Schellens JH Bevacizumab. Oncologist. 2010;15(8):819–825. doi:10.1634/theoncologist.2009-0317. ] [[Google Scholar]
- 189. Boydell E, Marinari E, Migliorini D, Dietrich PY, Patrikidou A, Dutoit V Exploratory study of the effect of IMA950/poly-ICLC vaccination on response to bevacizumab in relapsing high-grade glioma patients. Cancers (Basel). 2019;11(4):464. [Google Scholar]
- 190. Slingluff CL Jr., Petroni GR, Chianese-Bullock KA, Smolkin ME, Hibbitts S, Murphy C, Johansen N, Grosh WW, Yamshchikov GV, Neese PY, et al Immunologic and clinical outcomes of a randomized phase II trial of two multipeptide vaccines for melanoma in the adjuvant setting. Clin Cancer Res. 2007;13(21):6386–6395. doi:10.1158/1078-0432.CCR-07-0486. [] [[PubMed][Google Scholar]
- 191. Slingluff CL Jr., Petroni GR, Chianese-Bullock KA, Smolkin ME, Ross MI, Haas NB Randomized multicenter trial of the effects of melanoma-associated helper peptides and cyclophosphamide on the immunogenicity of a multipeptide melanoma vaccine. J Clin Oncol. 2011;29(21):2924–2932. doi:10.1200/JCO.2010.33.8053. ] [[Google Scholar]
- 192. Eaton MD, Scala AR Further observations on the inhibitory effect of myxoviruses on a transplantable murine leukemia. Proc Soc Exp Biol Med. 1969;132(1):20–26. doi:10.3181/00379727-132-34138. [] [[PubMed][Google Scholar]
- 193. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity. 1999;11(4):443–451. doi:10.1016/S1074-7613(00)80119-3. [] [[PubMed][Google Scholar]
- 194. Melssen MM, Petroni GR, Chianese-Bullock KA, Wages NA, Grosh WW, Varhegyi N A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund’s adjuvant in melanoma patients. J Immunother Cancer. 2019;7(1):163. doi:10.1186/s40425-019-0625-x. ] [[Google Scholar]
- 195. Aguilera D, MacDonald T, Castellino R, Janss A, Mazewski C, Kadom N, Pu M, Messer K, Crawford J, Connelly E, et al PDCT-03. A phase III trial of poly-ICLC in the management of recurrent or progressive pediatric low grade gliomas. Results for the neurofibromatosis 1 group. (NCT01188096). Neuro-Oncology. 2018;20(suppl_6):vi201. doi:10.1093/neuonc/noy148.833. [[PubMed][Google Scholar]
- 196. Ammi R, De Waele J, Willemen Y, Van Brussel I, Schrijvers DM, Lion E Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. Pharmacol Ther. 2015;146:120–131. doi:10.1016/j.pharmthera.2014.09.010. [] [[PubMed][Google Scholar]
- 197. Levy HB, Baer G, Baron S, Buckler CE, Gibbs CJ, Iadarola MJ A modified polyriboinosinic-polyribocytidylic acid complex that induces interferon in primates. J Infect Dis. 1975;132:434–439. [[PubMed][Google Scholar]
- 198. Rutz S, Wang X, Ouyang W The IL-20 subfamily of cytokines–from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14(12):783–795. doi:10.1038/nri3766. [] [[PubMed][Google Scholar]
- 199. Kuryk L, Moller AW, Jaderberg M Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. Oncoimmunology. 2019;8(2):e1532763. doi:10.1080/2162402X.2018.1532763. ] [[Google Scholar]
- 200. Kroemer G, Galluzzi L Combinatorial immunotherapy with checkpoint blockers solves the problem of metastatic melanoma-An exclamation sign with a question mark. Oncoimmunology. 2015;4(7):e1058037. doi:10.1080/2162402X.2015.1058037. ] [[Google Scholar]
- 201. Parmar A, Chan KKW, Ko YJ Metastatic colorectal cancer: therapeutic options for treating refractory disease. Curr Oncol. 2019;26(1):S24–S32. doi:10.3747/co.26.5575. ] [[Google Scholar]
- 202. Chow FC, Chok KS Colorectal liver metastases: an update on multidisciplinary approach. World J Hepatol. 2019;11(2):150–172. doi:10.4254/wjh.v11.i2.150. ] [[Google Scholar]
- 203. Kokoschka EM, Trautinger F, Knobler RM, Pohl-Markl H, Micksche M Long-term adjuvant therapy of high-risk malignant melanoma with interferon alpha 2b. J Invest Dermatol. 1990;95(6):193S–7S. doi:10.1111/1523-1747.ep12875517. [] [[PubMed][Google Scholar]
- 204. Li Y, Fang M, Zhang J, Wang J, Song Y, Shi J, Li W, Wu G, Ren J, Wang Z, et al Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumor immunity. Oncoimmunology. 2016;5(2):e1074374. doi:10.1080/2162402X.2015.1074374. ] [[Google Scholar]
- 205. Semeraro M, Adam J, Stoll G, Louvet E, Chaba K, Poirier-Colame V The ratio of CD8+/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ. Oncoimmunology. 2016;5(10):e1218106. doi:10.1080/2162402X.2016.1218106. ] [[Google Scholar]
- 206. Senovilla L, Vitale I, Martins I, Tailler M, Pailleret C, Michaud M, Galluzzi L, Adjemian S, Kepp O, Niso-Santano M, et al An immunosurveillance mechanism controls cancer cell ploidy. Science. 2012;337(6102):1678–1684. doi:10.1126/science.1224922. [] [[PubMed][Google Scholar]
- 207. Fridman WH, Zitvogel L, Sautes-Fridman C, Kroemer G The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 2017;14(12):717–734. doi:10.1038/nrclinonc.2017.101. [] [[PubMed][Google Scholar]
- 208. Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290. doi:10.1056/NEJMoa1712126. ] [[Google Scholar]
- 209. Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093–2104. doi:10.1056/NEJMoa1801946. ] [[Google Scholar]
- 210. Kverneland AH, Enevold C, Donia M, Bastholt L, Svane IM, Nielsen CH Development of anti-drug antibodies is associated with shortened survival in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology. 2018;7(5):e1424674. doi:10.1080/2162402X.2018.1424674. ] [[Google Scholar]
- 211. Madonna G, Ballesteros-Merino C, Feng Z, Bifulco C, Capone M, Giannarelli D PD-L1 expression with immune-infiltrate evaluation and outcome prediction in melanoma patients treated with ipilimumab. Oncoimmunology. 2018;7:e1405206. doi:10.1080/2162402X.2017.1405206. ] [[Google Scholar]
- 212. Wu X, Giobbie-Hurder A, Connolly EM, Li J, Liao X, Severgnini M, Zhou J, Rodig S, Hodi FS Anti-CTLA-4 based therapy elicits humoral immunity to galectin-3 in patients with metastatic melanoma. Oncoimmunology. 2018;7(7):e1440930. doi:10.1080/2162402X.2018.1440930. ] [[Google Scholar]
- 213. Castoldi F, Pietrocola F, Maiuri MC, Kroemer G Aspirin induces autophagy via inhibition of the acetyltransferase EP300. Oncotarget. 2018;9(37):24574–24575. doi:10.18632/oncotarget.25364. ] [[Google Scholar]
- 214. Pietrocola F, Castoldi F, Maiuri MC, Kroemer G Aspirin-another caloric-restriction mimetic. Autophagy. 2018;14(7):1162–1163. doi:10.1080/15548627.2018.1454810. ] [[Google Scholar]
- 215. Pietrocola F, Castoldi F, Markaki M, Lachkar S, Chen G, Enot DP Aspirin recapitulates features of caloric restriction. Cell Rep. 2018;22(9):2395–2407. doi:10.1016/j.celrep.2018.02.024. ] [[Google Scholar]
- 216. Vitale I, Sistigu A, Manic G, Rudqvist NP, Trajanoski Z, Galluzzi L Mutational and antigenic landscape in tumor progression and cancer immunotherapy. Trends Cell Biol. 2019;29(5):396–416. doi:10.1016/j.tcb.2019.01.003. [] [[PubMed][Google Scholar]
- 217. Buchan SL, Fallatah M, Thirdborough SM, Taraban VY, Rogel A, Thomas LJ, Penfold CA, He L-Z, Curran MA, Keler T, et al PD-1 blockade and CD27 stimulation activate distinct transcriptional programs that synergize for CD8+T-cell–driven antitumor immunity. Clin Cancer Res. 2018;24(10):2383–2394. doi:10.1158/1078-0432.CCR-17-3057. ] [[Google Scholar]
- 218. Aranda F, Vacchelli E, Eggermont A, Galon J, Fridman WH, Zitvogel L Trial watch: immunostimulatory monoclonal antibodies in cancer therapy. Oncoimmunology. 2014;3(2):e27297. doi:10.4161/onci.27297. ] [[Google Scholar]
- 219. Ansell SM. Pembrolizumab: living up to expectations. Blood. 2019;134(14):1114–1115. doi:10.1182/blood.2019002417. [] [[PubMed]
- 220. Anandasabapathy N, Breton G, Hurley A, Caskey M, Trumpfheller C, Sarma P, Pring J, Pack M, Buckley N, Matei I, et al Efficacy and safety of CDX-301, recombinant human Flt3L, at expanding dendritic cells and hematopoietic stem cells in healthy human volunteers. Bone Marrow Transplant. 2015;50(7):924–930. doi:10.1038/bmt.2015.74. ] [[Google Scholar]
- 221. Satyamitra M, Cary L, Dunn D, Holmes-Hampton GP, Thomas LJ, Ghosh SP CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice. Sci Rep. 2020;10(1):1757. doi:10.1038/s41598-020-58186-1. ] [[Google Scholar]
- 222. Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer. 2019;7(1):184. doi:10.1186/s40425-019-0662-5. ] [[Google Scholar]
- 223. Emens LA. Breast cancer immunotherapy: facts and hopes. Clin Cancer Res. 2018;24(3):511–520. doi:10.1158/1078-0432.CCR-16-3001. ] [
- 224. Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, Ganju V, Polikoff J, Saad F, Humanski P, et al Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J Clin Oncol. 2017;35(1):40–47. doi:10.1200/JCO.2016.69.1584. [] [[PubMed][Google Scholar]
- 225. Di Lorenzo G, Buonerba C, Kantoff PW Immunotherapy for the treatment of prostate cancer. Nat Rev Clin Oncol. 2011;8(9):551–561. doi:10.1038/nrclinonc.2011.72. [] [[PubMed][Google Scholar]
- 226. Drake CG. Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol. 2010;10(8):580–593. doi:10.1038/nri2817. ] [
- 227. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, et al Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–712. doi:10.1016/S1470-2045(14)70189-5. ] [[Google Scholar]
- 228. Costantini A, Julie C, Dumenil C, Helias-Rodzewicz Z, Tisserand J, Dumoulin J, Giraud V, Labrune S, Chinet T, Emile J-F, et al Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab. Oncoimmunology. 2018;7:e1452581. doi:10.1080/2162402X.2018.1452581. ] [[Google Scholar]
- 229. Lo SS, Fakiris AJ, Chang EL, Mayr NA, Wang JZ, Papiez L, Teh BS, McGarry RC, Cardenes HR, Timmerman RD, et al Stereotactic body radiation therapy: a novel treatment modality. Nat Rev Clin Oncol. 2010;7(1):44–54. doi:10.1038/nrclinonc.2009.188. [] [[PubMed][Google Scholar]
- 230. Bentebibel SE, Hurwitz ME, Bernatchez C, Haymaker C, Hudgens CW, Kluger HM, Tetzlaff MT, Tagliaferri MA, Zalevsky J, Hoch U, et al A first-in-human study and biomarker analysis of NKTR-214, a novel IL2Rbetagamma-biased cytokine, in patients with advanced or metastatic solid tumors. Cancer Discov. 2019;9(6):711–721. doi:10.1158/2159-8290.CD-18-1495. [] [[PubMed][Google Scholar]
- 231. Charych DH, Hoch U, Langowski JL, Lee SR, Addepalli MK, Kirk PB, Sheng D, Liu X, Sims PW, VanderVeen LA, et al NKTR-214, an engineered cytokine with biased IL2 receptor binding, increased tumor exposure, and marked efficacy in mouse tumor models. Clin Cancer Res. 2016;22(3):680–690. doi:10.1158/1078-0432.CCR-15-1631. [] [[PubMed][Google Scholar]
- 232. Boyman O, Sprent J The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12(3):180–190. doi:10.1038/nri3156. [] [[PubMed][Google Scholar]
- 233. Makarov DV, Carter HB The discovery of prostate specific antigen as a biomarker for the early detection of adenocarcinoma of the prostate. J Urol. 2006;176(6):2383–2385. doi:10.1016/j.juro.2006.08.019. [] [[PubMed][Google Scholar]
- 234. Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6:S13–8.
- 235. Shore ND, Morrow MP, McMullan T, Kraynyak KA, Sylvester A, Bhatt K, Cheung J, Boyer JD, Liu L, Sacchetta B, et al CD8+ T cells impact rising PSA in biochemically relapsed cancer patients using immunotherapy targeting tumor-associated antigens. Mol Ther. 2020;28(5):1238–1250. doi:10.1016/j.ymthe.2020.02.018. ] [[Google Scholar]
- 236. Aucouturier J, Dupuis L, Deville S, Ascarateil S, Ganne V Montanide ISA 720 and 51: a new generation of water in oil emulsions as adjuvants for human vaccines. Expert Rev Vaccines. 2002;1(1):111–118. doi:10.1586/14760584.1.1.111. [] [[PubMed][Google Scholar]
- 237. Turaj AH, Hussain K, Cox KL, MJJ R-Z, Testa J, Dahal LN, Chan HTC, James S, Field VL, Carter MJ, et al Antibody tumor targeting is enhanced by CD27 agonists through myeloid recruitment. Cancer Cell. 2017;32(6):777–91 e6. doi:10.1016/j.ccell.2017.11.001. ] [[Google Scholar]
- 238. Burris HA, Infante JR, Ansell SM, Nemunaitis JJ, Weiss GR, Villalobos VM, Sikic BI, Taylor MH, Northfelt DW, Carson WE, et al Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, in patients with advanced solid tumors. J Clin Oncol. 2017;35(18):2028–2036. doi:10.1200/JCO.2016.70.1508. [] [[PubMed][Google Scholar]
- 239. Starzer AM, Berghoff AS New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open. 2020;4(Suppl 3):e000629. doi:10.1136/esmoopen-2019-000629. ] [[Google Scholar]
- 240. Ciotti M, Angeletti S, Minieri M, Giovannetti M, Benvenuto D, Pascarella S, Sagnelli C, Bianchi M, Bernardini S, Ciccozzi M, et al COVID-19 outbreak: an overview. Chemotherapy. pp.1–9. 2020. doi:10.1159/000507423 ] [[Google Scholar]
- 241. Raoult D, Zumla A, Locatelli F, Ippolito G, Kroemer G Coronavirus infections: epidemiological, clinical and immunological features and hypotheses. Cell Stress. 2020;4(4):66–75. doi:10.15698/cst2020.04.216. ] [[Google Scholar]
- 242. Rothan HA, Byrareddy SN The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433. doi:10.1016/j.jaut.2020.102433. ] [[Google Scholar]