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- Title
CD39 expression defines exhausted CD4<sup>+</sup> T cells associated with poor survival and immune evasion in human gastric cancer.
- Authors
Duan, Zhen‐quan; Li, Yu‐xian; Qiu, Yuan; Shen, Yang; Wang, Ying; Zhang, Yuan‐yuan; Zhu, Bao‐hang; Yu, Xiao‐hong; Tan, Xue‐ling; Chen, Weisan; Zhuang, Yuan; Cheng, Ping; Zhang, Wei‐jun; Zou, Quan‐ming; Ma, Dai‐yuan; Peng, Liu‐sheng
- 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 cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.
- Subjects
T cells; T helper cells; REGULATORY T cells; STOMACH cancer; T-cell exhaustion
- Publication
Clinical & Translational Immunology, 2024, Vol 13, Issue 3, p1
- ISSN
2050-0068
- Publication type
Article
- DOI
10.1002/cti2.1499