High expression of B7-H3 on monocyte/macrophages in tumor microenvironment promotes lung cancer progression by inhibiting apoptosis

肿瘤微环境中单核细胞/巨噬细胞上 B7-H3 高表达通过抑制细胞凋亡促进肺癌进展

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作者:Dongze Zhang, Haitao Huang, Xin Gao, Gehua Yu, Xueguang Zhang, Haiyan Jin, Ruyan Xu, Zhenxin Wang, Guangbo Zhang

Abstract

Monocyte/macrophages constitute a significant population of tumor-infiltrating immune cells and play a crucial role in tumor growth, invasion, and metastasis. B7-H3, has immune regulatory functions, however, it is unclear whether B7-H3 expressed on monocyte/macrophages plays a significance role in tumor progression. We found B7-H3 was high-expressed on monocyte/macrophages in tumor microenvironment compared with adjacent tissues in lung cancer, and its expression level was positively correlated with the number of monocyte/macrophages. Furthermore, the expression of B7-H3 was related to clinical stage and lymph node metastasis. Moreover, miR-29a-3p negatively regulated B7-H3, and the expression of B7-H3 on THP-1-derived macrophages was regulated by secreting exosomes containing miR-29a-3p. In addition, knockdown of B7-H3 promoted macrophage apoptosis under hypoxia. Mechanistically, B7-H3 enhanced the antiapoptotic ability of macrophage by up-regulating HIF-1ɑ via activating NF-κB. Taken together, these results imply that B7-H3 as a therapeutic target could hold promise for enhancing anti-tumor immune responses in individuals diagnosed with lung cancer.

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