在胃癌中,CAFs通过基因素乳化介导的NCAPG无化抑制促进免疫逃避
Sheng Zhou1, Linmei Xiao2, Li Hu2
1Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi, 214000, Jiangsu Province, China.
Journal of translational medicine
|September 2, 2025
概括
癌症相关纤维细胞 (CAF) 通过乳酸分泌促进胃癌 (GC) 的进展和免疫逃避. 这项研究确定了H3K18la-ASPM-NCAPG轴和潜在的抑制剂Daturilin,以增强抗PD-1治疗.
科学领域:
- 癌症学
- 癌症生物学
- 免疫疗法
背景情况:
- 癌症相关纤维细胞 (CAF) 是瘤进展和免疫逃避的关键因素.
- 在瘤微环境中,CAF是乳酸的主要来源,影响癌症.
- 在胃癌 (GC) 免疫治疗中,CAF衍生的乳酸的作用尚不清楚.
研究的目的:
- 研究CAF衍生乳酸在胃癌进展和免疫逃避中的作用.
- 阐明GC中乳酸与抗PD-1抗性的分子机制.
- 确定增强免疫疗法的潜在治疗点.
主要方法:
- 用CUT&Tag和转录组测序来识别基因素乳化点.
- 共同免疫沉,质谱和分子对接以研究蛋白质相互作用.
- 在体外,体内和有机体实验验证拟议的机制.
主要成果:
- 从CAF中增加的乳酸在GC细胞中诱导H3K18乳化 (H3K18la).
- 作为H3K18la的标,ASPM促进了GC的进展和抗PD-1的抵抗.
- 通过SRC/ STAT3途径,ASPM- NCAPG相互作用对NCAPG的表达进行上调,从而增加PD- L1水平.
- 达图里林被确定为一种潜在的小分子抑制剂.
结论:
- 通过H3K18la-ASPM-NCAPG轴促进GC的进展.
- 这一轴有助于免疫逃避和抗PD-1治疗的抵抗.
- 达图里林有可能提高抗PD-1治疗的疗效.
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