LAUSR

MHC-II is known to be mainly expressed on the surface of antigen-presenting cells (APCs). Nevertheless, increasing evidence suggests that MHC-II is also expressed by solid tumor cancer cells and may be associated with better immunotherapy responses. However, the regulation of MHC-II in cancer cells remain unclear. In this study, we leveraged data mining and experimental validation to elucidate the regulation of MHC-II in cancer cells and its role in modulating the response to immunotherapy. We collated an extensive collection of omics data to examine the cancer-cell-intrinsic MHC-II expression and its association with immunotherapy outcomes. We then tested the functional relevance of cancer-cell-intrinsic MHC-II expression using a syngeneic transplantation model. Finally, we performed data mining to identify pathways potentially involved in the regulation of MHC-II expression, and experimentally validated candidate regulators. Comprehensive meta-analysis of multiomics data from an exhaustive collection of data revealed that MHC-II is heterogeneously expressed in various solid tumors, and its expression is particularly high in melanoma. Using a syngeneic transplantation model, we further established that melanoma cells with high MHC-II responded better to anti-PD-1 treatment. Data mining followed by experimental validation revealed the Hippo signaling pathway as a potential regulator of melanoma MHC-II expression. Citation Format: Shengqing Gu. Hippo signaling pathway regulates cancer-cell-intrinsic MHC-II expression in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2999.