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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 12/2018

01-12-2018 | Focussed Research Review

Splice variants of human natural cytotoxicity receptors: novel innate immune checkpoints

Authors: Avishai Shemesh, Michael Brusilovsky, Kiran Kundu, Aner Ottolenghi, Kerry S. Campbell, Angel Porgador

Published in: Cancer Immunology, Immunotherapy | Issue 12/2018

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Abstract

The natural cytotoxicity receptors (NCRs; NKp30, NKp44, and NKp46) were first defined as activating receptors on human NK cells that are important in recognition of and response to tumors. A flurry of recent research, however, has revealed that differential splicing can occur during transcription of each of the NCR genes, resulting in some transcripts that encode receptor isoforms with inhibitory functions. These alternative transcripts can arise in certain tissue microenvironments and appear to be induced by cytokines. Evidence indicates that some of the inhibitory NCRs are triggered by specific ligands, such as the interaction of the inhibitory isoform of NKp44 with PCNA on the surface of tumor cells. Here, we review the different NCR splice variants, cytokines that modulate their expression, their functional impacts on innate immune cells, and their differential expression in the contexts of cancer, pregnancy, and infections. The recent discovery of these inhibitory NCR isoforms has revealed novel innate immune checkpoints, many of which still lack defined ligands and clear mechanisms driving their expression. These NCR checkpoint pathways offer exciting potential therapeutic targets to manipulate innate immune functions under defined pathological conditions, such as cancer, pregnancy disorders, and pathogen exposure.
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Metadata
Title
Splice variants of human natural cytotoxicity receptors: novel innate immune checkpoints
Authors
Avishai Shemesh
Michael Brusilovsky
Kiran Kundu
Aner Ottolenghi
Kerry S. Campbell
Angel Porgador
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 12/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-2104-x

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