Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer
Background T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be fur...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000978.full |
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| author | Li Liu Quan Zhou Yifan Chen Weijuan Zhang Yu Xia Ying Xiong Yu Zhu Zewei Wang Han Zeng Hongyu Zhang Zhaopei Liu Qiuren Huang Jiajun Wang Yuan Chang Yiwei Wang Le Xu Bo Dai Qi Bai Jianming Guo Wenbin Jiang Zhiyuan Lin Yang Qu |
| author_facet | Li Liu Quan Zhou Yifan Chen Weijuan Zhang Yu Xia Ying Xiong Yu Zhu Zewei Wang Han Zeng Hongyu Zhang Zhaopei Liu Qiuren Huang Jiajun Wang Yuan Chang Yiwei Wang Le Xu Bo Dai Qi Bai Jianming Guo Wenbin Jiang Zhiyuan Lin Yang Qu |
| author_sort | Li Liu |
| collection | DOAJ |
| description | Background T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC).Methods 259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT+ CD8+ T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry.Results High infiltration of intratumoral TIGIT+ CD8+ T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT+ CD8+ cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT+ CD8+ T-cell abundance was correlated with impaired CD8+ T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT+ CD8+ T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils.Conclusion Intratumoral TIGIT+ CD8+ T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT+ CD8+ T-cell abundance correlated with dampened CD8+ T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT+ CD8+ T-cells. |
| format | Article |
| id | doaj-art-daa0a4df5566497d8f27239cd6c2da1a |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-daa0a4df5566497d8f27239cd6c2da1a2025-08-20T02:13:23ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-000978Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancerLi Liu0Quan Zhou1Yifan Chen2Weijuan Zhang3Yu Xia4Ying Xiong5Yu Zhu6Zewei Wang7Han Zeng8Hongyu Zhang9Zhaopei Liu10Qiuren Huang11Jiajun Wang12Yuan Chang13Yiwei Wang14Le Xu15Bo Dai16Qi Bai17Jianming Guo18Wenbin Jiang19Zhiyuan Lin20Yang Qu211 Outpatient, Shanghai Changning District Mental Health Center, Shanghai, ChinaDepartment of Dermatovenereology, Tianjin Medical University General Hospital/ Tianjin Institute of Sexually Transmitted Disease, Tianjin, China3 Department of Immunology, Fudan University School of Basic Medical Sciences, Shanghai, ChinaDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, ChinaAkeso Biopharma Co., Ltd., Zhongshan, Guangdong, China3 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China4 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, China1 Departments of Biochemistry and Molecular Biology, Fudan University School of Basic Medical Sciences, Shanghai, China2 Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaDepartment of Urology, Fudan University Shanghai Cancer Center, Shanghai, China1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China3 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Fudan University Shanghai Cancer Center, Shanghai, China4 Department of Urology, Shanghai Ninth People`s Hospital, Shanghai, ChinaDepartment of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China4 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China3 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China2 Department of Urology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaBackground T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC).Methods 259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT+ CD8+ T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry.Results High infiltration of intratumoral TIGIT+ CD8+ T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT+ CD8+ cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT+ CD8+ T-cell abundance was correlated with impaired CD8+ T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT+ CD8+ T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils.Conclusion Intratumoral TIGIT+ CD8+ T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT+ CD8+ T-cell abundance correlated with dampened CD8+ T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT+ CD8+ T-cells.https://jitc.bmj.com/content/8/2/e000978.full |
| spellingShingle | Li Liu Quan Zhou Yifan Chen Weijuan Zhang Yu Xia Ying Xiong Yu Zhu Zewei Wang Han Zeng Hongyu Zhang Zhaopei Liu Qiuren Huang Jiajun Wang Yuan Chang Yiwei Wang Le Xu Bo Dai Qi Bai Jianming Guo Wenbin Jiang Zhiyuan Lin Yang Qu Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer Journal for ImmunoTherapy of Cancer |
| title | Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer |
| title_full | Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer |
| title_fullStr | Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer |
| title_full_unstemmed | Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer |
| title_short | Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer |
| title_sort | intratumoral tigit cd8 t cell infiltration determines poor prognosis and immune evasion in patients with muscle invasive bladder cancer |
| url | https://jitc.bmj.com/content/8/2/e000978.full |
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