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骨髓系特异性膜蛋白LRRC25抑制了固体瘤的免疫力,是潜在的癌症免疫治疗检查点标

Guorong Zhang¹, Hanzhi Yu¹, Jingjing Liu¹

¹Tianjin Key Laboratory of Inflammatory Biology, Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China; State Key Laboratory of Experimental Hematology, Tianjin Medical University, Tianjin, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.

|April 25, 2025

概括

在髓状细胞上发现的含有白素的重复蛋白25 (LRRC25),通过重编程巨细胞来抑制瘤生长. 向LRRC25可以提高抗瘤免疫力和瘤微环境中的CD8+T细胞活性.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
细胞生物学细胞生物学

背景情况:

含有白素的重复蛋白25 (LRRC25) 是一种I型膜蛋白,在像中性粒细胞和巨细胞这样的髓状细胞中表达.
以前的研究表明LRRC25具有抗炎作用,但其在癌症免疫中的功能仍未被探索.

研究的目的:

研究LRRC25在癌症免疫中的作用,特别是其在瘤相关巨细胞 (TAMs) 中的表达和功能.
确定LRRC25是否可以作为癌症免疫治疗的潜在治疗标.

主要方法:

在瘤微环境 (TME) 内的瘤相关巨细胞 (TAMs) 中LRRC25表达的分析.
在Lrrc25缺乏的小鼠模型中评估瘤生长.
研究潜在的分子通路,包括Nox2-ROS-Nlrp3-Il1β通路.
评估免疫细胞的透和激活,特别是CD8+ T细胞.

主要成果:

在TAMs中,LRRC25的表达很高.
在多个小鼠模型中,TME中的Lrrc25缺乏抑制了瘤生长.
失去LRRC25将TAM重编程为抗瘤表型,增强CD8+T细胞透和激活.
发现Nox2-ROS-Nlrp3-Il1β通路在Lrrc25缺乏的TAM中升高.
LRRC25缺乏症在人类髓状细胞系或小鼠中没有引起异常,这表明它是一个安全的目标.

结论:

LRRC25在TME中充当免疫检查点,协调TAM活动.
通过Nlrp3-IL1β通路准LRRC25有望增强抗瘤免疫力和CD8+T细胞反应.
LRRC25代表了改善癌症免疫治疗结果的潜在治疗标.

关键词:

CP: 癌症癌症癌症 CP: 免疫学免疫学美国LRRC25 癌症免疫疗法免疫疗法膜蛋白是一种膜蛋白质.瘤微环境是一个微环境.与瘤相关的巨细胞.

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