CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response
BackgroundAs the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells’ roles in the anti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.865596/full |
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| author | Zhenghao Wu Zhenghao Wu Junjie Zhou Yunxiao Xiao Jie Ming Jing Zhou Fang Dong Xiaoqi Zhou Zhuoshuo Xu Xiangwang Zhao Ping Lei Tao Huang |
| author_facet | Zhenghao Wu Zhenghao Wu Junjie Zhou Yunxiao Xiao Jie Ming Jing Zhou Fang Dong Xiaoqi Zhou Zhuoshuo Xu Xiangwang Zhao Ping Lei Tao Huang |
| author_sort | Zhenghao Wu |
| collection | DOAJ |
| description | BackgroundAs the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells’ roles in the anti-tumor response are far from clear.MethodsBased on single-cell transcriptomic data for ICI-treated patients, we identified a B-cell cluster [BIR (ICI-Responsive B) cells] and described the phenotype, cell–cell communication, biological processes, gene signature, and prognosis value of BIR cells through bioinformatic analysis, tissue immunofluorescence, and animal experiments. Surgery samples from 12 non-small cell lung carcinoma (NSCLC) patients with adjuvant checkpoint blockade were evaluated as external validation.ResultsBIR cells were identified as a subset of CD20+CD22+ADAM28+ B cells with a memory phenotype. Bioinformatic analysis revealed that BIR cells had enhanced cell viability and epigenetic regulation, and that ALOX5AP, MIF, and PTPRC/CD45 expressed by myeloid cells may be critical coordinators of diverse biological processes of BIR cells. Immunofluorescence confirmed the presence of BIR cells in tertiary lymphoid structures (TLSs) in skin SCC, RCC, CRC, and breast cancer. BIR-associated gene signatures correlate with positive outcomes in patients with melanoma, glioblastoma, NSCLC, HNSCC, or RCC treated with ICI therapy, and BIR-cell density predicted NSCLC patients’ response to checkpoint immunotherapy. In line with this, melanoma-bearing mice depleted of BIR cells were resistant to ICIs.ConclusionsCD20+CD22+ADAM28+ BIR cells were present in cancer-associated TLS and promoted the response to ICI therapy. |
| first_indexed | 2024-04-13T09:11:50Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T09:11:50Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-18e5154b0b6d4020aeed3de5862dbc542022-12-22T02:52:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.865596865596CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy ResponseZhenghao Wu0Zhenghao Wu1Junjie Zhou2Yunxiao Xiao3Jie Ming4Jing Zhou5Fang Dong6Xiaoqi Zhou7Zhuoshuo Xu8Xiangwang Zhao9Ping Lei10Tao Huang11Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackgroundAs the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells’ roles in the anti-tumor response are far from clear.MethodsBased on single-cell transcriptomic data for ICI-treated patients, we identified a B-cell cluster [BIR (ICI-Responsive B) cells] and described the phenotype, cell–cell communication, biological processes, gene signature, and prognosis value of BIR cells through bioinformatic analysis, tissue immunofluorescence, and animal experiments. Surgery samples from 12 non-small cell lung carcinoma (NSCLC) patients with adjuvant checkpoint blockade were evaluated as external validation.ResultsBIR cells were identified as a subset of CD20+CD22+ADAM28+ B cells with a memory phenotype. Bioinformatic analysis revealed that BIR cells had enhanced cell viability and epigenetic regulation, and that ALOX5AP, MIF, and PTPRC/CD45 expressed by myeloid cells may be critical coordinators of diverse biological processes of BIR cells. Immunofluorescence confirmed the presence of BIR cells in tertiary lymphoid structures (TLSs) in skin SCC, RCC, CRC, and breast cancer. BIR-associated gene signatures correlate with positive outcomes in patients with melanoma, glioblastoma, NSCLC, HNSCC, or RCC treated with ICI therapy, and BIR-cell density predicted NSCLC patients’ response to checkpoint immunotherapy. In line with this, melanoma-bearing mice depleted of BIR cells were resistant to ICIs.ConclusionsCD20+CD22+ADAM28+ BIR cells were present in cancer-associated TLS and promoted the response to ICI therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.865596/fullB cellstertiary lymphoid structureimmunotherapyADAM28immune checkpoint inhibitors |
| spellingShingle | Zhenghao Wu Zhenghao Wu Junjie Zhou Yunxiao Xiao Jie Ming Jing Zhou Fang Dong Xiaoqi Zhou Zhuoshuo Xu Xiangwang Zhao Ping Lei Tao Huang CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response Frontiers in Immunology B cells tertiary lymphoid structure immunotherapy ADAM28 immune checkpoint inhibitors |
| title | CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response |
| title_full | CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response |
| title_fullStr | CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response |
| title_full_unstemmed | CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response |
| title_short | CD20+CD22+ADAM28+ B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response |
| title_sort | cd20 cd22 adam28 b cells in tertiary lymphoid structures promote immunotherapy response |
| topic | B cells tertiary lymphoid structure immunotherapy ADAM28 immune checkpoint inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.865596/full |
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