Front Immunol 11: 167

NK Cell-Based Immune Checkpoint Inhibition

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

^{Department of Oncology, The First Affiliated Hospital, Institute for Liver Diseases of Anhui Medical University, Hefei, China}

^{Department of Biochemistry, University of Sialkot, Sialkot, Pakistan}

Edited by: Jose A. Garcia-Sanz, Spanish National Research Council (CSIC), Spain

Reviewed by: Emanuela Marcenaro, University of Genoa, Italy; Raghvendra Mohan Srivastava, Memorial Sloan Kettering Cancer Center, United States

*Correspondence: Hua Wang nc.ude.umha@auhgnaw

This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

†These authors have contributed equally to this work

Edited by: Jose A. Garcia-Sanz, Spanish National Research Council (CSIC), Spain

Reviewed by: Emanuela Marcenaro, University of Genoa, Italy; Raghvendra Mohan Srivastava, Memorial Sloan Kettering Cancer Center, United States

Received 2019 Sep 9; Accepted 2020 Jan 21.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.

Keywords: natural killer cell (NK), cancer immunotherapy (CI), immune checkpoint inhibitors (ICI), immune checkpoint, immune therapeutics

Abstract

Immune checkpoint inhibition

ITIM-based inhibition and intracellular signaling in NK cells

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