BTN3A2在肿瘤中作用的研究进展

Research progress in the role of BTN3A2 in cancer

嗜乳脂蛋白亚家族3成员A2(lactophilin subfamily 3 member A2,BTN3A2)是一种与免疫系统相关的跨膜蛋白,其在B细胞、单核细胞和树突状细胞等免疫细胞中均有表达。近年来BTN3A2在肿瘤中的研究主要集中在三阴性乳腺癌、胰导管腺癌、卵巢上皮癌、肺腺癌、胃腺癌,其在多种肿瘤组织中呈差异表达。在干扰素-γ(interferonγ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)等促炎性细胞因子影响下表达可增加。BTN3A2通过调节T细胞介导的转录调节因子(T-box transcription factor,T-bet)、信号转导和转录激活因子(signal transducer and activator of transcription,STAT)1、IFN-γ、激活/或抑制核因子-κB(nuclear factor kappa B,NF-κB)、白介素-2(interleukin2,IL-2)/STAT3等信号通路增加肿瘤微环境中CD8^(+)、CD4^(+)T细胞和树突状细胞,通过诱导γδT细胞活化为Vγ9Vδ2 T细胞,从而可达到抗肿瘤作用。进一步的分析发现hsa-miR-17-5p可能是BTN3A2的miRNA靶点,这可为肿瘤的免疫治疗提供新思路。

Lactophilin subfamily 3 member A2(BTN3A2)is an immunologically relevant transmembrane protein and expressed in immune cells such as B cells,monocytes,and dendritic cells.In recent years,the studies of BTN3A2 in cancer primarily focus on triplenegative breast cancer,pancreatic ductal adenocarcinoma,ovarian epithelial carcinoma,lung adenocarcinoma,and gastric adenocarcinoma,where it exhibits differential expression in various tumor tissues.Its expression can be upregulated by pro-inflammatory cytokines like interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).BTN3A2 enhances CD8+and CD4+T cells and dendritic cells in tumor microenvironment by regulating T cell mediated transcription regulator factor T-bet,signal transducer and activator of transcription(STAT)1,IFN-γ;activation/inhibition of NF-κB signaling pathway,IL-2(interleukin-2)/STAT3 signaling pathway.By inducingγδT cells to activate into Vγ9Vδ2 T cells,anti-tumor effect can be achieved.Further analysis shows that hsa-miR-17-5p may be a miRNA target of BTN3A2,which may be provide new insights into cancerKEY WORDS lactophilin subfamily 3 member A2;cancer;immune response immunotherapy.