Mechanism of TCF21 Downregulation Leading to Immunosuppression of Tumor-Associated Macrophages in Non-Small Cell Lung Cancer

TCF21下调导致非小细胞肺癌肿瘤相关巨噬细胞免疫抑制的机制

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作者:Hong Liu, Run He, Xuliang Yang, Bo Huang, Hongxiang Liu

Abstract

Lung cancer, as one of the high-mortality cancers, seriously affects the normal life of people. Non-small cell lung cancer (NSCLC) accounts for a high proportion of the overall incidence of lung cancer, and identifying therapeutic targets of NSCLC is of vital significance. This study attempted to elucidate the regulatory mechanism of transcription factor 21 (TCF21) on the immunosuppressive effect of tumor-associated macrophages (TAM) in NSCLC. The experimental results revealed that the expression of TCF21 was decreased in lung cancer cells and TAM. Macrophage polarization affected T cell viability and tumor-killing greatly, and M2-type polarization reduced the viability and tumor-killing of CD8+T cells. Meanwhile, overexpression of TCF21 promoted the polarization of TAM to M1 macrophages and the enhancement of macrophages to the viability of T cells. Furthermore, there appears to be a targeting relationship between TCF21 and Notch, suggesting that TCF21 exerts its influence via the Notch signaling pathway. This study demonstrated the polarization regulation of TAM to regulate the immunosuppressive effect, which provides novel targets for the treatment of lung cancer.

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