NDLI: Retinoic acid enhances γδ T cell cytotoxicity in nasopharyngeal carcinoma by reversing immune exhaustion

Content Provider	Springer Nature : BioMed Central
Author	Liu, Guichao Quan, Qiang Pan, Lanhong Duan, Haibo Zhang, Guojun Li, Ke Zhu, Xinhai Zhang, Dongdong Li, Peng Zhao, Jianfu
Abstract	Recent studies have shown that the antitumor immunity of adaptive immune cells is regulated by Vitamin A (retinoic acid, RA). However, it remains unclear whether RA and retinoic acid receptor (RAR) signaling can modulate antitumor immunity by reversing immune exhaustion of innate-like γδ T cells in human nasopharyngeal carcinoma (NPC). Periphery blood samples from patients with NPC were prospectively collected, and phenotypic and functional analyses of γδ T cells were performed using flow cytometry. Tumor-bearing models and RAR inhibitor approaches were utilized to investigate RA/RAR-mediated regulation of T cell immunoglobulin domain and mucin domain 3 (Tim-3) and the antitumor activity of γδ T cells. Here, our findings indicate that immune exhaustion markers are highly expressed on peripheral αβ and γδ T cells in NPC patients. Serum RA levels are negatively correlated with the abundance of Tim-3 on circulating Vδ2 T cells. Mechanistic studies have demonstrated that RA/RAR signaling directly targets Vδ2 T cells, repressing Tim-3 expression, promoting NF-κB activation, and enhancing the production of antitumor-related cytokines. Notably, RA supplementation improved the efficacy of Vδ2 T cell-mediated immunotherapy in human NPC by suppressing Tim-3 expression. Collectively, these findings suggest that RA/RAR signaling plays a crucial role in reversing immune exhaustion and represents a promising target for γδ T cell antitumor immunotherapy.
Related Links	https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-025-02161-8.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12964-025-02161-8
Journal	Cell Communication and Signaling
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2025-03-29
Access Restriction	Open
Subject Keyword	Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors γδ T cells Retinoic acid Retinoic acid receptor Tim-3 Tumor immunity
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Molecular Biology
Journal Impact Factor	8.2/2023
5-Year Journal Impact Factor	8/2023

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