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CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer

Authors Zhu W, Zhao Z, Feng B, Yu W, Li J, Guo H, Yang R

Received 20 December 2020

Accepted for publication 3 March 2021

Published 25 March 2021 Volume 2021:14 Pages 2149—2161


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Arseniy Yuzhalin

Wenjie Zhu,1,* Zihan Zhao,1,* Baofu Feng,2 Wenhao Yu,3 Ji Li,3 Hongqian Guo,1 Rong Yang1

1Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing, 210008, People’s Republic of China; 2Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 3State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rong Yang; Hongqian Guo Email [email protected]; [email protected]

Introduction: Although immunotherapy works well in parts of patients with bladder cancer (BLCA), its overall response rate of anti-PD-1 inhibitors remains unsatisfactory. Besides, growing evidence shows that tumor-infiltrating lymphocytes (TILs) immunotherapy has demonstrated excellent efficacy in various cancers. Considering the huge heterogeneity and low overall survival rate of BLCA, it is urgent to explore the new immune checkpoints (ICs) or TILs therapy to improve the survival prognosis for BLCA patients.
Materials and Methods: The public bioinformatics databases were used to explore the prognostic value of 5 potential ICs targets (TIM-3, LAG-3, OX40, 4– 1BB and CD39). A total of 46 BLCA patients undergoing surgical treatment at our hospital from May 2020 to October 2020 were enrolled in this study. The expressions of PD-1, TIM-3, LAG-3, OX40, 4– 1BB, and CD39 in T cells of BLCA patients were explored by flow cytometry, and the correlation between different subgroups of T cells and clinicopathological parameters was analyzed. Besides, the mouse CD4+CD39+ T cells, CD4+CD39- T cells, CD8+CD39+ T cells, and CD8+CD39- T cells were sorted and co-cultured with MB49 bladder cancer cell lines in vitro to investigate the potential biomarker of tumor-reactive TILs.
Results: Public bioinformatics databases analyses show that only the high expression of CD39 was significantly associated with advanced tumor stage (P < 0.001) and tend to result in a worse survival rate. In our study, the elevated expression of CD39 in CD4+/CD8+ T cells were significantly associated with the pathological T stage (pT < 2, P = 0.041) and papillary tumor (P = 0.038). Moreover, the CD8+CD39+ T cells showed a stronger tumor-killing effect and produced a higher level of IFN-γ than other T cell populations.
Conclusion: CD39 may be a potential prognostic marker in BLCA, and CD8+CD39+ T cells may be selected as tumor-reactive and killing T cells for TILs therapy.

Keywords: CD8, CD39, T cells, anti-tumor cytotoxicity, bladder cancer, immunotherapy, TILs, immune checkpoint

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