Autophagy-mediated quality control of MHC class I molecules regulates tumor evasion

Antigen presentation by major histocompatibility complex class I (MHC class I) molecules is crucial for activating the T-cell-mediated immune response. A recent paper by Herhaus and colleagues revealed that IRGQ (immunity related GTPase Q) functions as an autophagy receptor for MHC class I molecules. IRGQ, being an oncogenic macroautophagy/autophagy receptor, also functions as an immune modulator, thus presenting a novel functional example. IRGQ regulates the quality control of MHC class I molecules, thereby influencing the T-cell-mediated immune response; IRGQ directs misfolded MHC class I molecules to autophagic degradation, thereby suppressing the immune response and mediating tumor evasion. Conversely, in the absence of IRGQ, free MHC class I heavy chains can reach the cell surface, potentially enhancing the immune response and suppressing tumor evasion. The results describe a novel example of autophagy promoting tumor evasion through immunomodulation. Indeed, the study found that lower levels of IRGQ are associated with higher survival rates in patients with hepatocellular carcinoma (HCC) and in a mouse model of HCC.