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CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer
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 v...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006912/ https://www.ncbi.nlm.nih.gov/pubmed/33790578 http://dx.doi.org/10.2147/OTT.S297272 |
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author | Zhu, Wenjie Zhao, Zihan Feng, Baofu Yu, Wenhao Li, Ji Guo, Hongqian Yang, Rong |
author_facet | Zhu, Wenjie Zhao, Zihan Feng, Baofu Yu, Wenhao Li, Ji Guo, Hongqian Yang, Rong |
author_sort | Zhu, Wenjie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8006912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-80069122021-03-30 CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer Zhu, Wenjie Zhao, Zihan Feng, Baofu Yu, Wenhao Li, Ji Guo, Hongqian Yang, Rong Onco Targets Ther Original Research 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. Dove 2021-03-25 /pmc/articles/PMC8006912/ /pubmed/33790578 http://dx.doi.org/10.2147/OTT.S297272 Text en © 2021 Zhu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Zhu, Wenjie Zhao, Zihan Feng, Baofu Yu, Wenhao Li, Ji Guo, Hongqian Yang, Rong CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer |
title | CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer |
title_full | CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer |
title_fullStr | CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer |
title_full_unstemmed | CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer |
title_short | CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer |
title_sort | cd8+cd39+ t cells mediate anti-tumor cytotoxicity in bladder cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006912/ https://www.ncbi.nlm.nih.gov/pubmed/33790578 http://dx.doi.org/10.2147/OTT.S297272 |
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