Abstract B076: Pan-cancer analysis to identify which cancers may benefit most from LAG-3 blockade

Immune checkpoint blockade using antibodies that target programmed-cell-death-1 (PD-1) or its ligand programmed-cell-death-ligand 1 (PD-L1), and/or cytotoxic-T-lymphocyte-associated-protein-4 (CTLA-4) have led to dramatic responses, but only in a subset of human cancers. An antibody targeting lymphocyte-activation-gene-3 (LAG-3), relatlimab (BMS-986016), recently showed significant clinical activity in melanoma, and early clinical data showed that LAG-3 expression is a biomarker of response to this agent. We performed a pan-cancer analysis of The Cancer Genome Atlas data to identify genomic and immunologic correlates of LAG-3 expression. Hyper-mutation, and exogenous (Epstein-Barr virus, human papillomavirus) or endogenous (endogenous retrovirus group 3 member 2) viral expression in tumor were associated with increased expression of LAG-3 in multiple cancer types. LAG-3 expression was also correlated with CD8A and PD-L1 expression in most cancer types; however, there were notable exceptions, including head-neck squamous-cell cancer (HNSC), renal cell cancer (RCC) and glioblastoma. In HNSC, LAG-3 expression, but not PD-L1, was significantly increased in HPV+ cancers. In RCC and gliobastoma, LAG-3 was more strongly associated with CD8A expression than PD-L1. These results may have implications on the design of future clinical trials of LAG-3 blockade. Citation Format: Shridar Ganesan, Anshuman Panda, Gyan Bhanot. Pan-cancer analysis to identify which cancers may benefit most from LAG-3 blockade [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B076.