德国法兰克福大学Ivan Dikic小组发现，IRGQ介导的自噬在MHC I类质量控制中促进肿瘤免疫逃逸。相关论文于2024年10月30日在线发表于国际学术期刊《细胞》。

研究人员展示了免疫相关GTP酶家族Q蛋白（IRGQ），一种至今未被表征的蛋白，其参与主要组织相容性复合体I类（MHC I类）分子的质量控制。IRGQ通过与GABARAPL2和LC3B的结合模式，将错误折叠的MHC I类引导至溶酶体降解。

在缺乏IRGQ的情况下，游离的MHC I重链不仅在细胞内积累，还被转运到细胞表面，从而促进免疫反应。患有肝细胞癌的小鼠和人类患者由于CD8+ T细胞对IRGQ敲除肿瘤细胞的反应性增加，显示出IRGQ水平降低的改善生存率。

因此，研究人员揭示了IRGQ作为MHC I类质量控制的调节因子，进而介导肿瘤免疫逃逸。

据了解，自噬-溶酶体系统负责降解多种货物，并且参与肿瘤进展。

附：英文原文

Title: IRGQ-mediated autophagy in MHC class I quality control promotes tumor immune evasion

Author: Lina Herhaus, Uxía Gestal-Mato, Vinay V. Eapen, Igor Mainkovi, Henry J. Bailey, Cristian Prieto-Garcia, Mohit Misra, Anne-Claire Jacomin, Aparna Viswanathan Ammanath, Ivan Bagari, Jolina Michaelis, Joshua Vollrath, Ramachandra M. Bhaskara, Georg Bündgen, Adriana Covarrubias-Pinto, Koraljka Husnjak, Jonathan Zller, Ajami Gikandi, Sara Ribii, Tobias Bopp, Gerbrand J. van der Heden van Noort, Julian D. Langer, Andreas Weigert, J. Wade Harper, Joseph D. Mancias, Ivan Dikic

Issue&Volume: 2024-10-30

Abstract: 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.

DOI: 10.1016/j.cell.2024.09.048

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01148-6