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化学致癌物:对癌症治疗的影响
Shaofeng Liu1, Mary Saunders1, Tak W Mak1,2,3,4
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
The Journal of clinical investigation
|October 16, 2023
概括
致癌物暴露通过减少M-CSF. 阻止瘤创造免疫抑制环境. 这导致抗瘤免疫细胞,提供新的癌症免疫治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 致癌物暴露与癌症免疫性增加有关,通常通过新抗原.
- 致癌物对免疫反应独立于新抗原的影响尚不清楚.
- 瘤微环境 (TME) 在癌症进展和免疫规避中发挥着关键作用.
研究的目的:
- 研究致癌物质对瘤微环境的新抗原独立作用.
- 阐明受致癌物治疗的癌细胞影响免疫反应的机制.
- 探索向致癌物诱导的免疫变化的潜力,用于癌症免疫疗法.
主要方法:
- 利用了暴露于致癌物质的癌细胞的细胞培养模型.
- 分析了关键细胞因子的表达,包括M-CSF (巨细胞殖民地刺激因子).
- 描述了瘤相关巨细胞 (TAMs) 的表型和功能.
- 在吸烟者和非吸烟者的肺癌样本中检查了TAM重编程.
主要成果:
- 用致癌物治疗的癌细胞显示M-CSF表达减少.
- 这种减少损害了免疫抑制性TME的建立.
- 在这种环境中,瘤相关巨细胞 (TAMs) 显示出抗瘤特性.
- 在吸烟者的人类肺癌中观察到TAM重编程,反映了实验发现.
结论:
- 暴露于致癌物质可以重编程TME,将TAM转向抗瘤表型.
- 减少的M-CSF是这种致癌物诱导的免疫重编程的关键调解者.
- 这些发现揭示了致癌物媒介癌症免疫性的一种新机制.
- 这种理解可能会为癌症免疫治疗的新策略提供信息.
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