Mincle通路调控的肿瘤相关巨噬细胞M2表型促进肿瘤血管生成的分子机制

本项目将研究巨噬细胞诱导C型凝集素Mincle通过调控肿瘤相关巨噬细胞（tumor-associated macrophage，TAM）M2表型变化促进肿瘤血管生成的分子机制。在前期研究中我们发现，肺癌肿瘤微环境中的Mincle/Syk/NF-κB信号环路帮助TAM维持M2免疫抑制表型。通过阻断TAM中的Mincle表达，可以有效抑制肿瘤生长、侵袭和转移。在进一步的研究中，我们通过RNA测序数据发现并初步验证了TAM中Mincle表达与肿瘤血管生成的联系，即Mincle通路激活促进血管内皮标志物CD31、血管内皮生长因子VEGFA及基质金属蛋白酶MMP9的表达。本研究将探究Mincle通路调控M2型TAM促进肿瘤血管生成的分子机制，这为我们更全面的了解Mincle调控的M2型TAM在促进肿瘤生长及微环境建立中的作用提供理论基础和实验依据。

This project will explore the molecular mechanism that Mincle promotes tumor angiogenesis by regulating the M2 phenotype of tumor-associated macrophages (TAMs). In our previous studies, we found that the Mincle/Syk/NF-κB signaling circuit in the tumor microenvironment of lung cancer helps TAMs to maintain M2 phenotype and immunosuppressive properties. By suppressing the expression of Mincle in TAMs, tumor growth, the invasive and metastatic activity can be effectively inhibited. As a further exploration, we discovered and preliminarily verified the association between the high Mincle expression in M2 TAMs and the increased level of angiogenesis based on the whole-transcriptional sequencing data, while the activation of the Mincle pathway increased the expression of CD31, VEGFA, and MMP9 as well. This project will explore the molecular and regulatory mechanisms of Mincle-induced M2 TAMs in promoting tumor angiogenesis, which will provide us with a scientific basis of Mincle-induced M2 TAMs in tumor growth and the development of the tumor immunosuppressive microenvironment.