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细胞焦亡调控肿瘤免疫微环境的分子机制研究进展
董婧,王耀,黄小侠,李林
沈阳农业大学 动物科学与医学学院, 沈阳 110866
摘要:
为探究细胞焦亡在肿瘤免疫微环境中的分子机制,收集国内外最新文献资料,对小动物肿瘤现状、细胞焦亡、诱导细胞焦亡的蛋白家族和其在肿瘤免疫微环境中的作用机制进行阐述。结果表明:1)细胞焦亡是由Gasdermins(GSDMs)家族蛋白所介导的可调节的细胞程序性死亡,GSDMs被蛋白酶水解激活,切割形成N端(具有成孔活性),在细胞膜上打孔,导致渗透性细胞裂解,从而将促炎分子释放到细胞外,引发炎症和免疫反应,对肿瘤微环境的调节有重要意义;2)细胞发生焦亡时会不断胀大破裂,释放细胞内容物,其产生的炎性环境可以招募细胞毒性T细胞(CD8+T)、巨噬细胞和NK细胞等免疫细胞杀死和吞噬肿瘤细胞,抑制髓源性抑制细胞(MDSC);3)细胞焦亡将肿瘤免疫微环境激活为免疫刺激状态,使其由“冷”转“热”,抑制肿瘤细胞的增殖、侵袭、转移,靶向治疗肿瘤疾病,降低患病宠物的死亡率。综上,诱导细胞焦亡和调控肿瘤免疫微环境为抗肿瘤治疗提供了新思路,细胞焦亡分子生物学机制的深入研究有望为宠物临床提供一种前景广阔的新型治疗方法。
关键词:  细胞焦亡  GSDMs蛋白家族  肿瘤免疫微环境  免疫细胞
DOI:10.11841/j.issn.1007-4333.2022.06.15
分类号:
基金项目:国家自然科学基金项目(32102736);辽宁省“兴辽英才计划”项目(XLYC1807120);沈阳中青年科技创新人才支持计划(RC200431);辽宁省高水平创新团队国外培养项目(2018LNGXJWPY-YB017);辽宁省普通本科高校际联合培养项目(2021-24)
Advances in molecular mechanisms of cell pyroptosis regulation of tumor immune microenvironment
DONG Jing,WANG Yao,HUANG Xiaoxia,LI Lin
College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
Abstract:
In order to explore the molecular mechanism of pyroptosis in tumor immune microenvironment, the research status of small animal tumors, pyroptosis, protein family that induce pyroptosis and their mechanism in the tumor immune microenvironment by collecting the latest literature was reviewed. The results showed that: 1)Pyroptosis is a regulated programmed cell death mediated by Gasdermins(GSDMs)proteins family. GSDMs are hydrolyzed and activated by proteases, cleaved to form N-terminals(with pore-forming activity), and punch holes in the cell membrane, resulting in lysis of permeable cells, so as to release pro-inflammatory molecules outside the cells, triggering inflammation and immune responses, which is of great significance for the regulation of tumor microenvironment. 2)The cells will swell and burst continuously when pyroptosis occurs, and release cell contents. The inflammatory environment can recruit cytotoxic T cells(CD8+T), macrophages, NK cells and other immune cells to kill and phagocytose tumor cells and inhibit myeloid-derived suppressor cells(MDSC). 3)Cell death activates the tumor immune microenvironment into an immune stimulation state, turning it from “cold” to “hot”, inhibiting the proliferation, invasion and metastasis of tumor cells, targeted treatment of tumor diseases and reducing the mortality of sick pets. In conclusion, inducing cell death and regulating tumor immune microenvironment provide new ideas for anti-tumor therapy. The in-depth study of the molecular biological mechanism of cell pyroptosis is expected to provide a promising new pet clinical treatment.
Key words:  pyroptosis  GSDMs protein family  tumor immune microenvironment  immune cells
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