The autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumor progression. Here, we show that the immunity-related GTPase family Q protein (IRGQ), an uncharacterized protein to date, acts in the quality control of major histocompatibility complex class I (MHC class I) molecules. IRGQ directs misfolded MHC class I toward lysosomal degradation through its binding mode to GABARAPL2 and LC3B. In the absence of IRGQ, free MHC class I heavy chains do not only accumulate in the cell but are also transported to the cell surface, thereby promoting an immune response. Mice and human patients suffering from hepatocellular carcinoma show improved survival rates with reduced IRGQ levels due to increased reactivity of CD8+ T cells toward IRGQ knockout tumor cells. Thus, we reveal IRGQ as a regulator of MHC class I quality control, mediating tumor immune evasion.

中文翻译：

---

IRGQ 介导的 MHC I 类质量控制自噬促进肿瘤免疫逃逸


自噬-溶酶体系统指导多种货物的降解，也参与肿瘤进展。在这里，我们表明免疫相关的 GTP 酶家族 Q 蛋白 （IRGQ） 是迄今为止未表征的蛋白质，在主要组织相容性复合物 I 类 （MHC I 类） 分子的质量控制中起作用。IRGQ 通过其与 GABARAPL2 和 LC3B 的结合模式，将错误折叠的 I 类 MHC 引导至溶酶体降解。在没有 IRGQ 的情况下，游离的 MHC I 类重链不仅在细胞中积累，而且还被转运到细胞表面，从而促进免疫反应。由于 CD8+ T 细胞对 IRGQ 敲除肿瘤细胞的反应性增加，患有肝细胞癌的小鼠和人类患者表现出更高的生存率和 IRGQ 水平降低。因此，我们揭示了 IRGQ 作为 MHC I 类质量控制的调节因子，介导肿瘤免疫逃逸。