Integrative Roles of NK Receptors and γδ TCRs in γδ T Cell-Mediated Cancer Immunity
Abstract
γδ T cells employ dual recognition strategies that integrate innate and adaptive immune sensing through NK receptors (NKRs) and γδ-TCRs in cancer immunity. Through the coordinated use of clonotypic γδ-TCRs and germline-encoded NKRs, γδ 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 γδ T cell subsets and how their signals are integrated with γδ-TCRs. We highlight subset-specific differential utilization of NKRs in circulating Vδ2 and tissue-resident Vδ1 γδ T cells, context-dependent integration of γδ-TCR and NKR signaling within the tumor microenvironment, and emerging implications for γδ T cell-based cancer immunotherapy.
Fields of Study & Subjects
Immune Cell Function and Interaction
T-cell and B-cell Immunology
Neuropeptides and Animal Physiology
Publication details
- Journal / source
- Immune Network
- Publisher
- XMLink
- Volume
- 26
- Issue
- 1
- Pages
- e3–e3
- Publication date
- 1 January 2026
- Language
- EN