暴露于致癌物质可以通过阻断免疫抑制瘤微环境的发展来增强癌症免疫性
Mei Huang1, Yun Xia1, Kaiwen Li1
1Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
The Journal of clinical investigation
|October 16, 2023
概括
暴露于化学致癌物质可以防止癌症产生免疫抑制性瘤微环境 (TME),从而导致T细胞排斥. 这种新抗原独立的效应涉及减少M-CSF,抑制免疫抑制性瘤相关巨细胞 (TAMs).
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,通常归因于新抗原生成.
- 致癌物质在塑造瘤微环境 (TME) 中的作用,与新抗原无关,目前尚不清楚.
研究的目的:
- 研究化学致癌物暴露对癌症的新抗原独立免疫学影响.
- 确定致癌物暴露是否影响瘤微环境 (TME) 和随后的癌症免疫性.
主要方法:
- 使用化学致癌物治疗的癌细胞缺乏额外的突变 (新抗原).
- 在小鼠体内评估T细胞中介排斥.
- 分析了M-CSF的表达和瘤相关巨细胞 (TAMs) 的存在.
- 对吸烟者和非吸烟者的人类肺癌样本进行单细胞分析.
主要成果:
- 暴露于致癌物质的癌细胞以T细胞依赖的方式被拒绝,即使没有新抗原.
- 与对照细胞的联合注射防止了排斥,突出了TME的作用.
- 致癌物治疗细胞中M-CSF表达的减少抑制了TAMs,导致免疫抑制性较低的TME.
- 与从未吸烟者相比,从前吸烟者的人类肺癌显示免疫抑制TAMs减少.
结论:
- 化学致癌物暴露会影响免疫抑制性TME的发展.
- 这种损伤导致T细胞介导的癌细胞排斥,独立于新抗原.
- 致癌物质通过调节TME和TAMs,代表了与癌症免疫性的一种新的联系.
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