膀癌免疫微环境在免疫检查点抑制反应的背景下
Jeroen van Dorp1, Michiel S van der Heijden1,2
1Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, Netherlands.
Frontiers in immunology
|September 20, 2023
概括
免疫检查点抑制剂 (ICI) 在肌肉侵入性膀癌 (BC) 中表现有前途. 它们的有效性取决于瘤免疫微环境 (TIME),包括免疫细胞透和三级淋巴体结构 (TLS).
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 肌肉侵入性膀癌 (BC) 通常用新辅助化疗和激进囊切除术治疗.
- 针对PD-1/PD-L1和CTLA-4的免疫检查点抑制剂 (ICI) 正在成为BC治疗的重大进展.
- 越来越多的人认为ICI的疗效受到瘤免疫微环境 (TIME) 的影响.
研究的目的:
- 探索瘤内在因素和确定膀癌中ICI反应的时间之间的复杂相互作用.
- 突出各种免疫细胞,三级淋巴体结构 (TLS),瘤突变负担 (TMB) 和癌症相关纤维细胞 (CAF) 在抗瘤免疫中的作用.
- 强调需要进一步研究ICI有效性背后的生物机制.
主要方法:
- 对膀癌治疗当前文献的综述,重点关注新辅助化疗,激进囊切除术和免疫检查点抑制剂.
- 分析瘤免疫微环境 (TIME) 的组成部分及其对抗瘤反应的影响.
- 讨论关键因素,如瘤突变负担 (TMB),免疫细胞透,三级淋巴体结构 (TLS) 和转化生长因子β (TGF-β) 信号传递.
主要成果:
- 膀癌中ICI的有效性受到时间的显著影响,包括CD8+T细胞,B细胞和巨细胞等免疫细胞的存在和活性.
- 三级淋巴体结构 (TLS) 与抗瘤免疫反应有关.
- 诸如高瘤突变负担 (TMB) 等因素促进抗瘤免疫力,而CAF中的TGF-β信号可以产生免疫抑制作用,阻碍淋巴细胞透.
结论:
- 免疫检查点抑制剂 (ICI) 在膀癌中的疗效是多因素的,这取决于瘤内在性质和瘤免疫微环境 (TIME).
- 了解TIME中的复杂相互作用对于优化ICI治疗至关重要.
- 对这些生物机制的进一步研究对于改善膀癌治疗患者的结果至关重要.
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