Genomic and immunologic correlates of LAG-3 expression in cancer.

Immune checkpoint blockade leads to unprecedented responses in many cancers. Although currently available agents mostly target the PD-1 and CTLA-4 pathways, agents targeting the immune checkpoint protein LAG-3 are under active clinical development, and early clinical data show that expression is a biomarker of response to LAG-3 blockade. To determine which cancers may benefit most from LAG-3 blockade, we performed a pan-cancer analysis of The Cancer Genome Atlas dataset to identify genomic and immunologic correlates of expression. High mutation burden, and expression of exogenous virus (EBV, HPV) or endogenous retrovirus (), were associated with overexpression of in multiple cancers. Although CD8 T-cell marker () and were strongly co-expressed with each other and with in most cancers, there were three notable exceptions: HPV+ head-neck squamous cell cancer, renal cell cancer, and glioblastoma. These results may have important implications for guiding development clinical trials of LAG-3 blockade.