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LRIG1激活了连接体VISTA,并损害了瘤特异性的CD8+T细胞反应

Hieu Minh Ta¹, Dia Roy¹, Keman Zhang¹

¹Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Science immunology

|May 17, 2024

概括

富含白的重复和免疫球蛋白样域1 (LRIG1) 通过结合V-域免疫球蛋白抑制T细胞激活 (VISTA) 作为抑制受体,抑制T细胞信号传递. 针对这个VISTA/LRIG1轴可能会增强癌症免疫疗法.

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:

免疫检查点封锁是癌症免疫治疗的关键策略.
维域免疫球蛋白抑制T细胞激活 (VISTA) 是一个免疫检查点目标,下游信号不清楚.
了解VISTA的监管机制对于改善癌症治疗至关重要.

研究的目的:

为了确定VISTA的下游信号合作伙伴.
阐明LRIG1在VISTA介导的免疫抑制中的作用.
评估向癌症中的VISTA/LRIG1轴的治疗潜力.

主要方法:

共同免疫沉以确定VISTA具有约束力的合作伙伴.
测试T细胞受体信号传递.
在体内研究使用T细胞特异性LRIG1淘汰小鼠.
对黑色素瘤患者透瘤的淋巴细胞的分析.

主要成果:

识别出富含白的重复和免疫球蛋白类域1 (LRIG1) 作为一个VISTA结合伙伴.
LRIG1作为一种抑制性受体,抑制T细胞受体信号传递.
在T细胞中删除LRIG1增强了抗瘤反应和CTL效应器功能.
在黑色素瘤患者中增加LRIG1表达与免疫疗法耐药性相关.

结论:

LRIG1作为一种新的抑制性免疫检查点受体.
维斯塔/LRIG1轴在调节T细胞对抗癌症反应方面发挥着重要作用.
准VISTA/LRIG1通路是提高癌症免疫治疗疗效的有希望的策略.

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