免疫治疗中与瘤控制相关的中性粒细胞反应
Jeremy Gungabeesoon1, Nicolas A Gort-Freitas2, Máté Kiss3
1Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.
Cell
|March 31, 2023
概括
成功的癌症免疫疗法扩大了对瘤控制至关重要的特定中性粒细胞. 这些治疗引起的中性粒细胞与人类患者共享干扰素特征,对于有效的抗瘤免疫是必不可少的.
科学领域:
- 免疫学
- 癌症学
- 癌症研究
背景情况:
- 中性粒细胞透到固体瘤, 往往与预后不佳相关.
- 透瘤的中性粒细胞是异质的,在癌症的进展和治疗中可能有不同的作用.
研究的目的:
- 研究中性粒细胞在有效的癌症免疫治疗和瘤控制中的特定作用.
- 确定参与成功抗瘤反应的中性粒细胞子集.
主要方法:
- 在免疫治疗期间对瘤中中性粒细胞群的分析.
- 评估中性粒细胞基因表达,包括干扰素刺激的基因.
- 调查特定的中性粒细胞因子的必要性,如IRF1,治疗疗效.
- 评估中性粒细胞对其他免疫成分 (如DC,IL-12,IFNγ) 的依赖性.
主要成果:
- 成功的免疫治疗会在瘤内急剧扩大特定的中性粒细胞子集 (Sellhi).
- 这些治疗引起的中性粒细胞表现出干扰素基因特征,与人类癌症患者观察到的基因特征相似.
- 中性粒细胞中转录因子IRF1的丧失会破坏免疫治疗的有效性.
- 中性粒细胞的反应取决于依赖BATF3的树突细胞,IL-12和IFNγ.
- 治疗后的全身中性粒细胞反应与肺癌患者的改善结果相关.
结论:
- 特定的中性粒细胞状态 (Sellhi) 对于有效的癌症免疫治疗至关重要.
- 治疗诱导的中性粒细胞具有干扰素特征,在瘤控制中发挥重要作用.
- 了解和调节这些中性粒细胞可以提高癌症治疗策略.
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