缺乏PRKCSH可通过UPR激活和M1巨细胞极化促进抗瘤免疫微环境
Guo Xiyuan1,2, Worapong Khaodee1, Yang Jianghua1,3
1Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Cancer cell international
|December 5, 2025
概括
肺腺癌中PRKCSH缺乏会破坏内质网膜应激反应,抑制免疫逃避并促进抗瘤免疫力. 准PRKCSH可能为肺癌提供一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 肺腺癌逃避免疫监测,并适应细胞内网膜 (ER) 的压力.
- IRE1α-XBP1通路对于ER应激感应至关重要,并影响瘤免疫微环境.
- 葡萄糖酶II的调节剂PRKCSH调节IRE1α活性,但其在瘤免疫中的作用尚不清楚.
研究的目的:
- 研究PRKCSH在肺腺癌中的免疫作用.
- 阐明PRKCSH如何影响ER压力信号和瘤免疫逃避.
主要方法:
- 临床样本分析和生物信息分析.
- 通过CRISPR/Cas9基因删除,细胞因子分析和巨细胞共同培养.
- 斑马鱼异种移植实验和细胞死亡途径的评估.
主要成果:
- 缺乏PRKCSH改变了ER应激反应,增加了XBP1s和p-JNK信号传递.
- PRKCSH淘汰 (KO) 抑制了IL-6和IL-8的分泌,增强了M1巨细胞的两极分化.
- 在体内,PRKCSH-KO细胞显示出亡和铁亡的增加,自功能受损,并促进了M1主导的免疫表型.
结论:
- 在肺腺癌中,PRKCSH是关键调节者,它将ER压力,瘤免疫逃避和细胞死亡途径与肺腺癌联系起来.
- 向PRKCSH可能是一种治疗策略,以增强铁和抗瘤免疫力.
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