Abstract 3724: Targeting the LIFR-LCN2 pathway to sensitize liver cancer to immunotherapy

Abstract Liver cancer, primarily hepatocellular carcinoma (HCC), is highly lethal with limited treatment options and no biomarker to predict therapy response. The current frontline therapies for liver cancer, including sorafenib and the combination of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF), have limited therapeutic benefits, which could be attributed, at least in part, to the highly immunosuppressive tumor microenvironment in liver cancer. Leukemia inhibitory factor receptor (LIFR) is frequently downregulated in HCC. My recent studies revealed that in oncogene-induced liver tumors, overexpression of LIFR increased, while knockout of Lifr decreased CD8+ T cell infiltration, which may be mediated by LCN2-dependent inhibition of T cell viability, proliferation, and effector function. In ongoing and future work, I will investigate whether LIFR or therapeutic LCN2 neutralization can sensitize HCC to immunotherapy. If successful, this project will illuminate how to improve liver cancer immunotherapy by targeting the LIFR-LCN2 pathway. Low LIFR expression and high LCN2 expression may be used to select HCC patients who will likely benefit from the combination therapy with the LCN2-neutralizing antibody plus immune checkpoint inhibitors. Citation Format: Yalan Deng, Li Ma. Targeting the LIFR-LCN2 pathway to sensitize liver cancer to immunotherapy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3724.