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分子生物学
IVD分子诊断
细胞培养与分析
蛋白研究
细胞因子
重组蛋白
抗体
高通量测序建库
病原检测UCF系列
生物医药
工具酶
抑制剂激活剂与常用试剂
仪器
耗材

Gasdermin D在PD-L1检查点阻断中限制抗肿瘤免疫的机制研究

Gasdermin D restricts anti-tumor immunity during PD-L1 checkpoint blockade

Yuying Jiang, Yongbing Yang, Yingchao Hu, Rui Yang, Jiajia Huang, Yi Liu, Yuqing Wu, Sheng Li, Chunmei Ma, Fiachra Humphries, Bingwei Wang, Xi Wang, Zhibin Hu, Shuo Yang

Journal:Cell Reports

IF:10

DOI:10.1016/j.celrep.2022.111553

PMID:36288704

Published:2022-10-25

research field:代谢工程药学微生物学生物技术

Abstract

Summary Tumor microenvironments (TMEs) require co-operation of innate and adaptive immune cells, which influence tumor progression and immunotherapy. Caspase-activated gasdermins facilitate tumor death and promote anti-tumor immunity. How pyroptosis in immune cells affects the TME remains unclear. TME expression of gasdermin D (GSDMD) is highly expressed in antigen-presenting cells (APCs) and correlates with immune checkpoint signatures. Through conditional deletion of GSDMD, we demonstrate that GSDMD in TME APCs restricts anti-tumor immunity during PD-L1 inhibition. Loss of GSDMD in APCs enhances interferon-stimulated genes (ISGs), thereby promoting CD8 + T cell activation in a cGAS-dependent manner. Moreover, pharmacological inhibition of GSDMD-mediated pyroptosis and PD-L1 improve anti-tumor immunity, highlighting the potential of combining GSDMD/PD-L1 inhibition for immunotherapy as a therapeutic strategy.

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