非典型的记忆B细胞在肝细胞癌中获得Breg表型
Shi Yong Neo1,2, Timothy Wai Ho Shuen3, Shruti Khare4
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
瘤微环境塑造了肝癌中的B细胞. 一些B细胞变得抑制性,可能充当调节性B细胞 (Bregs) 并抑制肝细胞癌 (HCC) 中的抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 瘤透淋巴细胞B细胞 (TIL-B) 具有功能性可塑性,有助于抗瘤反应和免疫抑制.
- 瘤微环境 (TME) 对TIL-B发育的影响仍然被低估,特别是在肝细胞癌 (HCC) 中.
研究的目的:
- 描述HCC TME中的TIL-B表型和克隆性.
- 调查HCC TME通过哪些机制影响B细胞功能并促进免疫抑制的机制.
主要方法:
- 集成的单细胞转录组学和B细胞受体 (BCR) 测序以配置TIL-B.
- 采用轨迹和基因调控网络分析来了解B细胞分化的途径.
- 评估HCC瘤细胞对周围血液B细胞的功能影响.
主要成果:
- 在HCC TME.内确定了不同的B细胞种群 (血,记忆,天真).
- 揭示了血细胞和炎症记忆B细胞的一个子集中BCR信号的下调.
- 具有抑制性,与年龄相关的B细胞表型 (TBET+CD11c+),表达PD-L1,CD25和B粒酶.
- 证明HCC瘤细胞在外围B细胞中诱导抑制功能,抑制T细胞共刺激.
结论:
- 在涉及TIL-B的HCC中阐明了非正规免疫抑制的新机制.
- 在HCC TME和外周血液中的非典型记忆B细胞可以作为调节性B细胞 (Bregs) 起作用.
- 这些发现凸显了B细胞在塑造HCC的免疫格局方面发挥的关键作用.
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