巨噬细胞极化
癌症研究
肿瘤微环境
免疫系统
肺癌
免疫疗法
血管生成
巨噬细胞
癌症免疫疗法
医学
免疫学
体内
生物
体外
内科学
生物技术
生物化学
作者
Juliang Qin,Xiaoyu Zhang,Binghe Tan,Su Zhang,Chengcong Yin,Qi Xue,Zhen Zhang,Hua Ren,Jinlian Chen,Mingyao Liu,Min Qian,Bing Du
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2020-09-15
卷期号:8 (11): 1426-1439
被引量:50
标识
DOI:10.1158/2326-6066.cir-20-0123
摘要
Abstract P2X7, a crucial sensor of extracellular ATP, is widely distributed in different immune cells as a potent stimulant of inflammation and immunity. P2X7 is also highly expressed in immunosuppressive cells such as tumor-associated macrophages (TAM) and even tumor cells. However, the function and potential applications of P2X7-mediated immunosuppressive responses in the tumor microenvironment remain unclear. Here, we demonstrated that P2X7 was highly expressed in TAMs and that P2X7 deficiency impaired the “M2-like” polarization of TAMs via downregulation of STAT6 and IRF4 phosphorylation both in vivo and in vitro. P2X7 deficiency restricted the progression of urethane-induced lung carcinogenesis and Lewis lung cancer by decreasing tumor cell proliferation and angiogenesis, promoting T-cell mobilization, and reversing M2-like TAM polarization. Thus, deletion or blockade of P2X7 was therapeutic for lung cancer. Furthermore, resistance to both immunotherapy (anti–PD-1 antibody) and chemotherapy (cisplatin) was overcome by coadministration of the P2X7 inhibitors O-ATP, A-438079 hydrochloride, and A-740003. Therefore, our data revealed a vital role of P2X7 in tumor formation through regulating TAM polarization, suggesting the therapeutic potential of P2X7 blockade in patients with lung cancer.
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