Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD ‐1/ PD‐L1 pathway in multiple myeloma

作者：Jiangbo Zhang, Zhaoyun Liu, Panpan Cao, Hao Wang, Hui Liu, Luoming Hua, Hua Xue, Rong Fu · 发表于：Cancer Medicine · 年份：2022 · DOI：10.1002/cam4.4814 · 被引用次数：17 · 研究领域：Immune cells in cancer、Multiple Myeloma Research and Treatments、Cancer Immunotherapy and Biomarkers

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 si...