CD39 expression defines exhausted CD4 + T cells associated with poor survival and immune evasion in human gastric cancer

作者：Zhen‐quan Duan, Yu-Xian Li, Yuan Qiu, Yang Shen, Ying Wang, Yuan‐yuan Zhang, Bao‐hang Zhu, YU Xiao-hong, Xue‐ling Tan, Weisan Chen, Yuan Zhuang, Ping Cheng, Weijun Zhang, Quanming Zou, Daiyuan Ma, Liu‐sheng Peng · 发表于：Clinical & Translational Immunology · 年份：2024 · DOI：10.1002/cti2.1499 · 被引用次数：7 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers

Abstract Objectives CD4 + T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4 + T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4 + T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4 + T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results In comparison with CD4 + T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4 + T cells expressed CD39. Most GC‐infiltrating CD39 + CD4 + T cells exhibited CD45RA − CCR7 − effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39 − CD4 + counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39 + CD4 + T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion Our study demonstrates that CD39 expression defines GC‐infiltrating CD4 + T c...