调节抗瘤免疫力的B细胞特异检查点分子
Lloyd Bod1,2,3,4, Yoon-Chul Kye1,2,3, Jingwen Shi1,2,5
1Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Nature
|June 21, 2023
概括
研究人员发现一种特定的B细胞子集在黑色素瘤生长过程中扩大. 向这种TIM-1表达B细胞子集显著抑制瘤生长并增强抗瘤免疫力.
科学领域:
- 免疫学
- 癌症学
- 细胞生物学
背景情况:
- 在抗瘤免疫中B细胞的作用尚未完全理解.
- 目前的免疫疗法主要针对T细胞和自然杀手细胞.
研究的目的:
- 研究B细胞在黑色素瘤进展过程中的抗瘤免疫力.
- 确定参与瘤生长和免疫反应的特定B细胞子集.
主要方法:
- 高通量流细胞计
- 大量和单细胞RNA测序
- B细胞受体测序
- 在B16F10黑色素瘤生长过程中对B细胞的分析
主要成果:
- 在排水淋巴结中确定了表达T细胞免疫球蛋白和粘素域1 (TIM-1) 的B细胞的扩张子集.
- 这一子组还表达了PD-1,TIM-3,TIGIT和LAG-3等共抑制分子.
- 在B细胞中选择性删除TIM-1 (Havcr1) 抑制了瘤生长并增强了T细胞反应.
- 损失TIM-1增强了1型干扰素反应,增加了B细胞激活,抗原呈现和共刺激,导致瘤特异性T细胞扩张.
结论:
- 在调节抗瘤免疫力方面,表达TIM-1的B细胞起着至关重要的作用.
- 针对B细胞的TIM-1可以增强适应性免疫力并抑制瘤生长.
- 这突显了一种新的癌症免疫疗法策略,
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