Integrative Roles of NK Receptors and γδ TCRs in γδ T Cell-Mediated Cancer Immunity

초록

gamma 8 T cells employ dual recognition strategies that integrate innate and adaptive immune sensing through NK receptors (NKRs) and gamma 8 gamma 8-TCRs in cancer immunity. Through the coordinated use of clonotypic gamma 8 gamma 8-TCRs and germline-encoded NKRs, gamma 8 T cells recognize malignant cells in an MHC-unrestricted manner and exert potent cytotoxic and immunomodulatory functions. In this review, we discuss how activating and inhibitory NKRs-including NKG-2D, natural cytotoxicity receptors, CD16, NKG-2A, and killer cell immunoglobulin-like receptors-are expressed across major human gamma 8 T cell subsets and how their signals are integrated with gamma 8 gamma 8-TCRs. We highlight subset-specific differential utilization of NKRs in circulating V82 and tissue-resident V81 gamma 8 T cells, context-dependent integration of gamma 8 gamma 8-TCR and NKR signaling within the tumor microenvironment, and emerging implications for gamma 8 T cell-based cancer immunotherapy.

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