B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer
Abstract Negative immune checkpoint blockade immunotherapy has shown potential for multiple malignancies including colorectal cancer (CRC). B7-H5, a novel negative immune checkpoint regulator, is highly expressed in tumor tissues and promotes tumor immune escape. However, the clinical significance o...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-09-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00628-4 |
| _version_ | 1819138301946232832 |
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| author | Jiayu Wang Hongya Wu Yanjun Chen Jinghan Zhu Linqing Sun Juntao Li Zhendong Yao Yuqi Chen Xueguang Zhang Suhua Xia Weichang Chen Tongguo Shi |
| author_facet | Jiayu Wang Hongya Wu Yanjun Chen Jinghan Zhu Linqing Sun Juntao Li Zhendong Yao Yuqi Chen Xueguang Zhang Suhua Xia Weichang Chen Tongguo Shi |
| author_sort | Jiayu Wang |
| collection | DOAJ |
| description | Abstract Negative immune checkpoint blockade immunotherapy has shown potential for multiple malignancies including colorectal cancer (CRC). B7-H5, a novel negative immune checkpoint regulator, is highly expressed in tumor tissues and promotes tumor immune escape. However, the clinical significance of B7-H5 expression in CRC and the role of B7-H5 in the tumor microenvironment (TME) has not been fully clarified. In this study, we observed that high B7-H5 expression in CRC tissues was significantly correlated with the lymph node involvement, AJCC stage, and survival of CRC patients. A significant inverse correlation was also observed between B7-H5 expression and CD8+ T-cell infiltration in CRC tissues. Kaplan−Meier analysis showed that patients with high B7-H5 expression and low CD8+ T-cell infiltration had the worst prognosis in our cohort of CRC patients. Remarkably, both high B7-H5 expression and low CD8+ T infiltration were risk factors for overall survival. Additionally, B7-H5 blockade using a B7-H5 monoclonal antibody (B7-H5 mAb) effectively suppressed the growth of MC38 colon cancer tumors by enhancing the infiltration and Granzyme B production of CD8+ T cells. Importantly, the depletion of CD8+ T cells obviously abolished the antitumor effect of B7-H5 blockade in the MC38 tumors. In sum, our findings suggest that B7-H5 may be a valuably prognostic marker for CRC and a potential target for CRC immunotherapy. |
| first_indexed | 2024-12-22T11:04:36Z |
| format | Article |
| id | doaj.art-2eef37d6c8aa47428fba2c1ad0db747f |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-22T11:04:36Z |
| publishDate | 2021-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-2eef37d6c8aa47428fba2c1ad0db747f2022-12-21T18:28:22ZengNature Publishing GroupCell Death Discovery2058-77162021-09-01711810.1038/s41420-021-00628-4B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancerJiayu Wang0Hongya Wu1Yanjun Chen2Jinghan Zhu3Linqing Sun4Juntao Li5Zhendong Yao6Yuqi Chen7Xueguang Zhang8Suhua Xia9Weichang Chen10Tongguo Shi11Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Soochow UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityDepartment of Oncology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityAbstract Negative immune checkpoint blockade immunotherapy has shown potential for multiple malignancies including colorectal cancer (CRC). B7-H5, a novel negative immune checkpoint regulator, is highly expressed in tumor tissues and promotes tumor immune escape. However, the clinical significance of B7-H5 expression in CRC and the role of B7-H5 in the tumor microenvironment (TME) has not been fully clarified. In this study, we observed that high B7-H5 expression in CRC tissues was significantly correlated with the lymph node involvement, AJCC stage, and survival of CRC patients. A significant inverse correlation was also observed between B7-H5 expression and CD8+ T-cell infiltration in CRC tissues. Kaplan−Meier analysis showed that patients with high B7-H5 expression and low CD8+ T-cell infiltration had the worst prognosis in our cohort of CRC patients. Remarkably, both high B7-H5 expression and low CD8+ T infiltration were risk factors for overall survival. Additionally, B7-H5 blockade using a B7-H5 monoclonal antibody (B7-H5 mAb) effectively suppressed the growth of MC38 colon cancer tumors by enhancing the infiltration and Granzyme B production of CD8+ T cells. Importantly, the depletion of CD8+ T cells obviously abolished the antitumor effect of B7-H5 blockade in the MC38 tumors. In sum, our findings suggest that B7-H5 may be a valuably prognostic marker for CRC and a potential target for CRC immunotherapy.https://doi.org/10.1038/s41420-021-00628-4 |
| spellingShingle | Jiayu Wang Hongya Wu Yanjun Chen Jinghan Zhu Linqing Sun Juntao Li Zhendong Yao Yuqi Chen Xueguang Zhang Suhua Xia Weichang Chen Tongguo Shi B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer Cell Death Discovery |
| title | B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer |
| title_full | B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer |
| title_fullStr | B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer |
| title_full_unstemmed | B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer |
| title_short | B7-H5 blockade enhances CD8+ T-cell-mediated antitumor immunity in colorectal cancer |
| title_sort | b7 h5 blockade enhances cd8 t cell mediated antitumor immunity in colorectal cancer |
| url | https://doi.org/10.1038/s41420-021-00628-4 |
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