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SIRPG表达与炎症瘤微环境和对PD-1封锁反应具有积极的关联

Libo Luo¹, Minlin Jiang¹, Hong Wu²

¹Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China.

Cancer immunology, immunotherapy : CII

|June 4, 2024

概括

高信号调节蛋白玛 (SIRPG) 表达与炎症瘤免疫微环境相关,并预测在NSCLC和黑色素瘤等癌症中对PD-1阻塞治疗的更好反应.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
遗传学遗传学是一个

背景情况:

研究信号调节蛋白 (SIRPG) 在癌症免疫中的作用.
了解SIRPG对瘤免疫微环境 (TME) 表型和T细胞介导的抗瘤免疫的影响.
评估SIRPG对对编程细胞死亡蛋白1 (PD-1) 阻断疗法的反应的预测价值.

研究的目的:

探索SIRPG表达和TME表型之间的关联.
为了确定SIRPG是否预测癌症患者对PD-1阻塞的反应.
阐明SIRPG在T细胞免疫中的功能作用.

主要方法:

使用转录基因数据对SIRPG表达和免疫解的泛癌分析.
分析了157名非小细胞肺癌 (NSCLC) 和黑色素瘤患者的转录和临床数据,这些患者接受了PD-1阻断治疗.
单细胞RNA测序 (scRNA-seq) 用于研究SIRPG表达特征.
在体外实验涉及SIRPG在Jurkat T细胞中被淘汰或过度表达的实验.

主要成果:

高SIRPG表达与增加的T细胞,B细胞,NK细胞,M1巨细胞和细胞毒性淋巴细胞有关,以及增强的免疫调节因子.
相反,高的SIRPG与较低的中性粒细胞,M2巨细胞和髓状细胞衍生的抑制细胞相关.
在高SIRPG表达率的NSCLC和黑色素瘤患者中观察到对PD-1阻断的有利反应.
scRNA-seq在CD8+耗尽的T细胞和CD4+调节性T细胞中揭示了SIRPG表达,与免疫检查点表达积极相关 (PDCD1,CTLA4).
实验室研究证实,SIRPG可以促进T细胞中PDCD1和CTLA4的表达.

结论:

高SIRPG表达意味着癌症中的炎症免疫表型.
SIRPG作为PD-1阻断治疗反应的有希望的预测生物标志物.
SIRPG代表了癌症免疫治疗的潜在新目标.

关键词:

生物标志物生物标志物肺癌是一种肺癌.在PD-1中使用PD-1.编程细胞死亡1受体受体斯里尔普格 (SIRPG) 是一个国际通讯员.瘤微环境是一个微环境.

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