Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma
Abstract Background Tumor‐associated macrophages (TAMs) are originated from circulating mononuclear cells in peripheral blood. They result from the recruitment of tumor cells and are a vital constituent of the tumor microenvironment. TAMs may be involved in the immunological escape of vicious clonal...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4814 |
| _version_ | 1828114749121888256 |
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| author | Jiangbo Zhang Zhaoyun Liu Panpan Cao Hao Wang Hui Liu Luoming Hua Hua Xue Rong Fu |
| author_facet | Jiangbo Zhang Zhaoyun Liu Panpan Cao Hao Wang Hui Liu Luoming Hua Hua Xue Rong Fu |
| author_sort | Jiangbo Zhang |
| collection | DOAJ |
| description | Abstract Background Tumor‐associated macrophages (TAMs) are originated from circulating mononuclear cells in peripheral blood. They result from the recruitment of tumor cells and are a vital constituent of the tumor microenvironment. TAMs may be involved in the immunological escape of vicious clonal plasma cells (PC) in the bone marrow (BM) of sufferers with myeloma. Methods From March 2020 to January 2021, 28 healthy controls (HC) and 86 multiple myeloma (MM) (53 newly diagnosed MM [NDMM] and 33 remissions) patients were enrolled as objects of the study. The expression of TAMs in the BM, CSF1 on CD138 + cells, and CSF1R on macrophages were detected by the method of flow cytometry, and the expression of PD‐1 on CD8 + T cells and PD‐L1 on TAMs were also done. Bone marrow mononuclear cells (BMMNCs) were extracted and cultured into TAMs, CD8 + T cells were sorted by magnetic beads and cultured, a coculture system was established and different inhibitors were added. The expression of the perforin and granzyme B was detected by flow cytometry. Results The percentage of TAMs in NDMM group (61.49 ± 2.176%) increased when compared with remission (23.08 ± 1.699%, p < 0.001) and HC group (17.95 ± 1.865%, p < 0.001), and TAMs decreased after adding CSF1R inhibitor. Moreover, the expression of CSF1 on CD138 + cells increased significantly in NDMM group (17.090 ± 0.9156%) than remission (8.214 ± 0.5911% p < 0.001), and HC group (5.257 ± 0.6231%, p < 0.001), and CSF1R on macrophages increased significantly in NDMM group (58.78 ± 2.286%) than remission (20.74 ± 1.376%, p < 0.001) and HC group (17.42 ± 1.081%, p < 0.001). The expression of PD‐1 on CD8 + T cells in NDMM group (32.64 ± 2.982%) increased than remission (20.35 ± 2.335% p < 0.01) and HC group (17.53 ± 1.349%, p < 0.001), and PD‐L1 on TAMs also increased in NDMM group (50.92 ± 2.554%) than remission (20.02 ± 1.893%, p < 0.001) and HC group (13.08 ± 1.289%, p < 0.001). When CD8 + T cells were cocultured with TAMs, the perforin and granzyme B levels decreased significantly. However, the perforin and granzyme B levels were partly restored after adding CSF1R inhibitor and anti‐PD‐L1 antibody. Conclusion Our study shows that TAMs were increased in MM patients which can inhibit the function of cytotoxic T lymphocyte (CTL) through the PD‐1/ PD‐L1 signaling pathway and participate in the occurrence of immune escape of myeloma cells. |
| first_indexed | 2024-04-11T12:30:44Z |
| format | Article |
| id | doaj.art-f72383fd322b49d0b729afd386a3667c |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-11T12:30:44Z |
| publishDate | 2022-12-01 |
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| series | Cancer Medicine |
| spelling | doaj.art-f72383fd322b49d0b729afd386a3667c2022-12-22T04:23:47ZengWileyCancer Medicine2045-76342022-12-0111244838484810.1002/cam4.4814Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myelomaJiangbo Zhang0Zhaoyun Liu1Panpan Cao2Hao Wang3Hui Liu4Luoming Hua5Hua Xue6Rong Fu7Department of Hematology Tianjin Medical University General Hospital Tianjin People's Republic of ChinaDepartment of Hematology Tianjin Medical University General Hospital Tianjin People's Republic of ChinaDepartment of Hematology Tianjin Medical University General Hospital Tianjin People's Republic of ChinaDepartment of Hematology Tianjin Medical University General Hospital Tianjin People's Republic of ChinaDepartment of Hematology Tianjin Medical University General Hospital Tianjin People's Republic of ChinaDepartment of Hematology Hebei University Affiliated Hospital Baoding People's Republic of ChinaDepartment of Hematology Hebei University Affiliated Hospital Baoding People's Republic of ChinaDepartment of Hematology Tianjin Medical University General Hospital Tianjin People's Republic of ChinaAbstract Background Tumor‐associated macrophages (TAMs) are originated from circulating mononuclear cells in peripheral blood. They result from the recruitment of tumor cells and are a vital constituent of the tumor microenvironment. TAMs may be involved in the immunological escape of vicious clonal plasma cells (PC) in the bone marrow (BM) of sufferers with myeloma. Methods From March 2020 to January 2021, 28 healthy controls (HC) and 86 multiple myeloma (MM) (53 newly diagnosed MM [NDMM] and 33 remissions) patients were enrolled as objects of the study. The expression of TAMs in the BM, CSF1 on CD138 + cells, and CSF1R on macrophages were detected by the method of flow cytometry, and the expression of PD‐1 on CD8 + T cells and PD‐L1 on TAMs were also done. Bone marrow mononuclear cells (BMMNCs) were extracted and cultured into TAMs, CD8 + T cells were sorted by magnetic beads and cultured, a coculture system was established and different inhibitors were added. The expression of the perforin and granzyme B was detected by flow cytometry. Results The percentage of TAMs in NDMM group (61.49 ± 2.176%) increased when compared with remission (23.08 ± 1.699%, p < 0.001) and HC group (17.95 ± 1.865%, p < 0.001), and TAMs decreased after adding CSF1R inhibitor. Moreover, the expression of CSF1 on CD138 + cells increased significantly in NDMM group (17.090 ± 0.9156%) than remission (8.214 ± 0.5911% p < 0.001), and HC group (5.257 ± 0.6231%, p < 0.001), and CSF1R on macrophages increased significantly in NDMM group (58.78 ± 2.286%) than remission (20.74 ± 1.376%, p < 0.001) and HC group (17.42 ± 1.081%, p < 0.001). The expression of PD‐1 on CD8 + T cells in NDMM group (32.64 ± 2.982%) increased than remission (20.35 ± 2.335% p < 0.01) and HC group (17.53 ± 1.349%, p < 0.001), and PD‐L1 on TAMs also increased in NDMM group (50.92 ± 2.554%) than remission (20.02 ± 1.893%, p < 0.001) and HC group (13.08 ± 1.289%, p < 0.001). When CD8 + T cells were cocultured with TAMs, the perforin and granzyme B levels decreased significantly. However, the perforin and granzyme B levels were partly restored after adding CSF1R inhibitor and anti‐PD‐L1 antibody. Conclusion Our study shows that TAMs were increased in MM patients which can inhibit the function of cytotoxic T lymphocyte (CTL) through the PD‐1/ PD‐L1 signaling pathway and participate in the occurrence of immune escape of myeloma cells.https://doi.org/10.1002/cam4.4814CD8 + T cellsCSF1Rmultiple myelomaPD‐1/PD‐L1TAMs |
| spellingShingle | Jiangbo Zhang Zhaoyun Liu Panpan Cao Hao Wang Hui Liu Luoming Hua Hua Xue Rong Fu Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma Cancer Medicine CD8 + T cells CSF1R multiple myeloma PD‐1/PD‐L1 TAMs |
| title | Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma |
| title_full | Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma |
| title_fullStr | Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma |
| title_full_unstemmed | Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma |
| title_short | Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma |
| title_sort | tumor associated macrophages regulate the function of cytotoxic t lymphocyte through pd 1 pd l1 pathway in multiple myeloma |
| topic | CD8 + T cells CSF1R multiple myeloma PD‐1/PD‐L1 TAMs |
| url | https://doi.org/10.1002/cam4.4814 |
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