Data from Thymosin α-1 Reverses M2 Polarization of Tumor-Associated Macrophages during Efferocytosis

• DOI: 10.1158/0008-5472.c.6513729.v1
• Publication Date: 2023-03-31T21:18:48Z
• Authors: 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
• Keywords: efferocytosis

<div>Abstract<p>The immunologic effects of chemotherapy-induced tumor cell death are not completely understood. Accumulating evidence suggests that phagocytic clearance apoptotic cells, also known as efferocytosis, is an immunologically silent process, thus maintaining immunosuppressive microenvironment (TME). Here we report that, in the breast microenvironment, thymosin α-1 (Tα-1) significantly reverses M2 polarization IL10-producing tumor-associated macrophages (TAM) during efferocytosis induced by cells. Mechanistically, Tα-1, which bound to phosphatidylserine on surface cells and was internalized macrophages, triggered activation SH2-containing inositol 5′-phosphatase 1 (SHIP1) through lysosomal Toll-like receptor 7 (TLR7)/MyD88 pathway, subsequently resulting dephosphorylation efferocytosis-activated TBK1 reduction efferocytosis-induced IL10. Tα-1 combined with epirubicin chemotherapy markedly suppressed growth <i>in vivo</i> cancer model reducing macrophage-derived IL10 enhancing number function tumor-infiltrating CD4<sup>+</sup> CD8<sup>+</sup> T In conclusion, improved curative effect reversing suggesting injection immediately after may contribute highly synergistic antitumor patients cancer.</p>Significance:<p>Thymosin improves via a TLR7/SHIP1 axis.</p></div>