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集成的BATF转录网络调节抑制性内调节性T细胞

Feng Shan^1,2,3, Anthony R Cillo^1,3, Carly Cardello^1,3

¹Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Science immunology

|September 15, 2023

概括

研究人员确定了一种特定类型的调节性T细胞 (T_reg) 丰富在瘤中,称为TNFR⁺ T_regs. 转录因子BATF控制这些细胞,为癌症治疗提供潜在的点,而不会破坏免疫平衡.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
分子生物学分子生物学

背景情况:

人类调节性T细胞 (T_regs) 对于免疫平衡至关重要,但由于其抑制功能,在癌症治疗中存在挑战.
区分瘤特异性T_regs对于开发向癌症治疗而不会损害整体免疫功能至关重要.
控制内T_regs的转录程序及其与外围T_regs的差异尚未得到充分理解.

研究的目的:

与健康组织相比,在瘤透调节性T细胞 (T_regs) 中识别不同的转录程序.
研究特定的转录因子和细胞表面分子在内T_regs的功能和丰富中的作用.
探索癌症治疗的潜在治疗标,可以选择性地抑制促进瘤的Tregs.

主要方法:

单细胞RNA测序CD4⁺ T细胞从头部和部状细胞癌 (HNSCC) 瘤,外周血液和健康的捐赠组织.
瘤丰富的T_regs表达瘤死亡因子受体 (TNFR) 基因 (TNFR⁺ T_regs) 亚群的识别和表征.
用CRISPR-Cas9基因编辑来评估转录因子BATF在人类激活的T_regs中的功能,随后进行RNA测序和功能测试.

主要成果:

确定了TNFR⁺ T_regs的一个亚群,并发现它们在HNSCC患者的瘤微环境 (TME) 中具有高度丰富性.
TNFR⁺ T_regs的存在与HNSCC和其他固体瘤的更差预后相关.
转录因子BATF被确定为TNFR⁺T_regs的关键调节者,控制它们的激活,存活和基因表达.
确定了一组与内T_regs的BATF驱动网络相关的表面分子.

结论:

BATF是高度抑制内T_regs的关键调节者.
TNFR⁺T_regs代表了一个独特的T_reg子集,在瘤中丰富,并与不良预后相关.
准BATF或相关的表面分子可能为癌症免疫疗法提供一种可以节省免疫平衡的策略.

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