CD39 hi identifies an exhausted tumor-reactive CD8 + T cell population associated with tumor progression in human gastric cancer.

Autor: Shen Y; Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, China; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China., Qiu Y; Department of General Surgery, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China., Duan ZQ; Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, China; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China., Li YX; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China., Wang Y; Department of General Surgery, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China., Zhang YY; Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, China; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China., Zhu BH; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China., Yu XH; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China; College of Pharmacy, Chongqing University of Technology, Chongqing 400038, China., Tan XL; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China; College of Pharmacy, Chongqing University of Technology, Chongqing 400038, China., Chen W; Department of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, Australia., Zhuang Y; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China., Zou QM; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China. Electronic address: qmzou@tmmu.edu.cn., Ma DY; Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, China. Electronic address: mdylx@163.com., Peng LS; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China. Electronic address: pengliusheng06@163.com.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2024 Apr; Vol. 202, pp. 107122. Date of Electronic Publication: 2024 Feb 29.
DOI: 10.1016/j.phrs.2024.107122
Abstrakt: The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8 + T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8 + T cells contained a fraction of CD39 hi cells that constituted about 6.6% of total CD8 + T cells in tumors. These CD39 hi cells enriched for GC-infiltrating CD8 + T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39 hi CD8 + T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39 int and CD39 - CD8 + counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39 hi CD8 + T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39 hi CD8 + T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8 + T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39 hi CD8 + T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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