基化疗诱导免疫疗法反应相关的空间和流体生物标志物在膀癌微环境对立的影响
Maksim A Chelushkin1,2,3, Jeroen van Dorp1,4, Sandra van Wilpe5
1Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
概括
基于的化疗改变了尿路癌的瘤微环境,影响免疫细胞和信号通路. 这些复杂的变化可能解释了临床试验中对联合免疫疗法的不一致反应.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 基于的化疗和免疫检查点抑制剂是晚期泌尿器癌的标准治疗方法.
- 由于临床试验结果不一致,这些疗法的最佳整合尚不清楚.
- 化疗对瘤免疫微环境的影响尚不清楚.
研究的目的:
- 研究基化疗如何调节瘤免疫微环境.
- 探索对免疫检查点抑制剂反应的潜在临床影响.
主要方法:
- 在116名尿路膀癌患者中分析了免疫细胞密度和空间关系.
- 评估了基化疗前后的配对样本.
- 评估了瘤和 stromal 组件的变化.
主要成果:
- 化疗增加了内CD8+T细胞百分比和PDL1+免疫细胞.
- 观察到纤维细胞介导的TGFβ信号传递增加和免疫细胞与癌细胞之间的距离增加.
- 特定的疗法影响了巨细胞 (MVAC) 和纤维细胞TGFβ信号传递 (gemcitabine).
结论:
- 基于的化疗对瘤免疫微环境有相反的影响.
- 这些复杂的调制可能解释了尿路癌中联合化疗和免疫治疗的可变反应.
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