Thymosin α-1 reverses M2 polarization of tumor-associated macrophages during efferocytosis
Thymosin α-1 reverses M2 polarization of tumor-associated macrophages during efferocytosis
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发表时间：
2022
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通讯作者：
Li-Xin Wang
中科院分区：
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作者：
Yi-Ting Wei;Xu-Ru Wang;Chunguang Yan;Fang Huang;Yunpeng Zhang;Xueming Liu;Zhi-Fa Wen;Xiao-Tong Sun;Yue Zhang;Yong-Qiang Chen;Rong Gao;Ning Pan;Li-Xin Wang
The immunologic effects of chemotherapy-induced tumor cell death are not completely understood. Accumulating evidence suggests that phagocytic clearance of apoptotic tumor cells, also known as efferocytosis, is an immunologically silent process, thus maintaining an immunosuppressive tumor microenvironment.(TME). Here we report that, in the breast tumor microenvironment, thymosin a-1 (Ta-1) significantly reverses M2 polarization of IL10-producing tumor-associated macrophages (TAM) during efferocytosis induced by apoptotic cells. Mechanistically, Ta-1, which bound to phosphatidylserine on the surface of.apoptotic tumor cells and was internalized by macrophages, triggered the activation of SH2-containing inositol 50 -phosphatase 1 (SHIP1) through the lysosomal Toll-like receptor 7 (TLR7)/ MyD88 pathway, subsequently resulting in dephosphorylation of efferocytosis-activated TBK1 and reduction of efferocytosisinduced IL10. Ta-1 combined with epirubicin chemotherapy markedly suppressed tumor growth in an in vivo breast cancer model by reducing macrophage-derived IL10 and enhancing the number and function of tumor-infiltrating CD4þ and CD8þ T cells. In conclusion, Ta-1 improved the curative effect of chemotherapy by reversing M2 polarization of efferocytosisactivated macrophages, suggesting that Ta-1 injection immediately after themotherapy may contribute to highly synergistic antitumor effects in patients with breast cancer.
