S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma
Abstract Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi‐omics analysis identified S100A5 as a novel immunosuppressive...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202300110 |
| _version_ | 1827824739898359808 |
|---|---|
| author | Huihuang Li Jinbo Chen Zhenghao Li Minfeng Chen Zhenyu Ou Miao Mo Ruizhe Wang Shiyu Tong Peihua Liu Zhiyong Cai Chunyu Zhang Zhi Liu Dingshan Deng Jinhui Liu Chunliang Cheng Jiao Hu Xiongbing Zu |
| author_facet | Huihuang Li Jinbo Chen Zhenghao Li Minfeng Chen Zhenyu Ou Miao Mo Ruizhe Wang Shiyu Tong Peihua Liu Zhiyong Cai Chunyu Zhang Zhi Liu Dingshan Deng Jinhui Liu Chunliang Cheng Jiao Hu Xiongbing Zu |
| author_sort | Huihuang Li |
| collection | DOAJ |
| description | Abstract Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi‐omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro‐inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti‐PD‐1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real‐world and several public immunotherapy cohorts. In summary, S100A5 shapes a non‐inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro‐inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA. |
| first_indexed | 2024-03-12T02:32:03Z |
| format | Article |
| id | doaj.art-93d943543f234e55a0ab440f97643444 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T02:32:03Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-93d943543f234e55a0ab440f976434442023-09-05T07:49:09ZengWileyAdvanced Science2198-38442023-09-011025n/an/a10.1002/advs.202300110S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder CarcinomaHuihuang Li0Jinbo Chen1Zhenghao Li2Minfeng Chen3Zhenyu Ou4Miao Mo5Ruizhe Wang6Shiyu Tong7Peihua Liu8Zhiyong Cai9Chunyu Zhang10Zhi Liu11Dingshan Deng12Jinhui Liu13Chunliang Cheng14Jiao Hu15Xiongbing Zu16Department of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaHunan Provincial Key Laboratory of Hepatobiliary Disease Research and Division of Hepato‐Biliary‐Pancreatic Surgery Department of General Surgery The Second Xiangya Hospital Central South University Changsha 410011ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaDepartment of Urology Xiangya Hospital Central South University Changsha 410008ChinaAbstract Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi‐omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro‐inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti‐PD‐1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real‐world and several public immunotherapy cohorts. In summary, S100A5 shapes a non‐inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro‐inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA.https://doi.org/10.1002/advs.202300110bladder carcinomaeffector immune cellsimmunotherapyS100 familytumor microenvironment |
| spellingShingle | Huihuang Li Jinbo Chen Zhenghao Li Minfeng Chen Zhenyu Ou Miao Mo Ruizhe Wang Shiyu Tong Peihua Liu Zhiyong Cai Chunyu Zhang Zhi Liu Dingshan Deng Jinhui Liu Chunliang Cheng Jiao Hu Xiongbing Zu S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma Advanced Science bladder carcinoma effector immune cells immunotherapy S100 family tumor microenvironment |
| title | S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma |
| title_full | S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma |
| title_fullStr | S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma |
| title_full_unstemmed | S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma |
| title_short | S100A5 Attenuates Efficiency of Anti‐PD‐L1/PD‐1 Immunotherapy by Inhibiting CD8+ T Cell‐Mediated Anti‐Cancer Immunity in Bladder Carcinoma |
| title_sort | s100a5 attenuates efficiency of anti pd l1 pd 1 immunotherapy by inhibiting cd8 t cell mediated anti cancer immunity in bladder carcinoma |
| topic | bladder carcinoma effector immune cells immunotherapy S100 family tumor microenvironment |
| url | https://doi.org/10.1002/advs.202300110 |
| work_keys_str_mv | AT huihuangli s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT jinbochen s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT zhenghaoli s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT minfengchen s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT zhenyuou s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT miaomo s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT ruizhewang s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT shiyutong s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT peihualiu s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT zhiyongcai s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT chunyuzhang s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT zhiliu s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT dingshandeng s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT jinhuiliu s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT chunliangcheng s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT jiaohu s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma AT xiongbingzu s100a5attenuatesefficiencyofantipdl1pd1immunotherapybyinhibitingcd8tcellmediatedanticancerimmunityinbladdercarcinoma |