Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade
Abstract Tumor‐associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleuki...
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Wiley
2023-04-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.242 |
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| author | Cheng Xu Yu Xia Bai‐Wei Zhang Emmanuel Kwateng Drokow Hua‐Yi Li Sen Xu Zhen Wang Si‐Yuan Wang Ping Jin Tian Fang Xiao‐Ming Xiong Pu Huang Ning Jin Jia‐Hong Tan Qing Zhong Yu‐Xin Chen Qi Zhang Yong Fang Fei Ye Qing‐Lei Gao |
| author_facet | Cheng Xu Yu Xia Bai‐Wei Zhang Emmanuel Kwateng Drokow Hua‐Yi Li Sen Xu Zhen Wang Si‐Yuan Wang Ping Jin Tian Fang Xiao‐Ming Xiong Pu Huang Ning Jin Jia‐Hong Tan Qing Zhong Yu‐Xin Chen Qi Zhang Yong Fang Fei Ye Qing‐Lei Gao |
| author_sort | Cheng Xu |
| collection | DOAJ |
| description | Abstract Tumor‐associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleukin (IL)‐1β was among the most abundant cytokines within the in vitro tumor‐macrophage coculture system, and enhanced IL‐1β expression was associated with impaired cytotoxicity of CD8+ T cells in human ovarian cancer, indicating the possibility that IL‐1β mediated immunosuppression during tumor‐TAMs crosstalk. Mechanistically, we demonstrated that IL‐1β significantly boosted programmed death‐ligand 1 (PD‐L1) expression in tumor cells via the activation of the nuclear factor‐κb signaling cascade. Specifically, IL‐1β released from TAMs was triggered by lactate, the anaerobic metabolite of tumor cells, in an inflammasome activation‐dependent manner. IL‐1β sustained and intensified immunosuppression by promoting C‐C motif chemokine ligand 2 secretion in tumor cells to fuel TAMs recruitment. Importantly, IL‐1β neutralizing antibody significantly curbed tumor growth and displayed synergistic antitumor efficacies with anti‐PD‐L1 antibody in tumor‐bearing mouse models. Together, this study presents an IL‐1β‐centered immunosuppressive loop between TAMs and tumor cells, highlighting IL‐1β as a candidate therapeutic target to reverse immunosuppression and potentiate immune checkpoint blockade. |
| format | Article |
| id | doaj-art-506d4057a846426198a400319a03e8f0 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-506d4057a846426198a400319a03e8f02025-01-24T05:36:29ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.242Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockadeCheng Xu0Yu Xia1Bai‐Wei Zhang2Emmanuel Kwateng Drokow3Hua‐Yi Li4Sen Xu5Zhen Wang6Si‐Yuan Wang7Ping Jin8Tian Fang9Xiao‐Ming Xiong10Pu Huang11Ning Jin12Jia‐Hong Tan13Qing Zhong14Yu‐Xin Chen15Qi Zhang16Yong Fang17Fei Ye18Qing‐Lei Gao19Department of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Radiation Oncology Zhengzhou University People's Hospital & Henan Provincial People's Hospital Zhengzhou ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Obstetrics and Gynecology The Second Affiliated Hospital Wenzhou Medical University Wenzhou ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Obstetrics and Gynecology The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Plastic and Cosmetic Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Gynecological Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract Tumor‐associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleukin (IL)‐1β was among the most abundant cytokines within the in vitro tumor‐macrophage coculture system, and enhanced IL‐1β expression was associated with impaired cytotoxicity of CD8+ T cells in human ovarian cancer, indicating the possibility that IL‐1β mediated immunosuppression during tumor‐TAMs crosstalk. Mechanistically, we demonstrated that IL‐1β significantly boosted programmed death‐ligand 1 (PD‐L1) expression in tumor cells via the activation of the nuclear factor‐κb signaling cascade. Specifically, IL‐1β released from TAMs was triggered by lactate, the anaerobic metabolite of tumor cells, in an inflammasome activation‐dependent manner. IL‐1β sustained and intensified immunosuppression by promoting C‐C motif chemokine ligand 2 secretion in tumor cells to fuel TAMs recruitment. Importantly, IL‐1β neutralizing antibody significantly curbed tumor growth and displayed synergistic antitumor efficacies with anti‐PD‐L1 antibody in tumor‐bearing mouse models. Together, this study presents an IL‐1β‐centered immunosuppressive loop between TAMs and tumor cells, highlighting IL‐1β as a candidate therapeutic target to reverse immunosuppression and potentiate immune checkpoint blockade.https://doi.org/10.1002/mco2.242immune checkpoint blockadeinterleukin‐1βprogrammed death‐ligand 1tumor‐immune microenvironmenttumor‐associated macrophages |
| spellingShingle | Cheng Xu Yu Xia Bai‐Wei Zhang Emmanuel Kwateng Drokow Hua‐Yi Li Sen Xu Zhen Wang Si‐Yuan Wang Ping Jin Tian Fang Xiao‐Ming Xiong Pu Huang Ning Jin Jia‐Hong Tan Qing Zhong Yu‐Xin Chen Qi Zhang Yong Fang Fei Ye Qing‐Lei Gao Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade MedComm immune checkpoint blockade interleukin‐1β programmed death‐ligand 1 tumor‐immune microenvironment tumor‐associated macrophages |
| title | Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade |
| title_full | Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade |
| title_fullStr | Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade |
| title_full_unstemmed | Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade |
| title_short | Macrophages facilitate tumor cell PD‐L1 expression via an IL‐1β‐centered loop to attenuate immune checkpoint blockade |
| title_sort | macrophages facilitate tumor cell pd l1 expression via an il 1β centered loop to attenuate immune checkpoint blockade |
| topic | immune checkpoint blockade interleukin‐1β programmed death‐ligand 1 tumor‐immune microenvironment tumor‐associated macrophages |
| url | https://doi.org/10.1002/mco2.242 |
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