LAG3 (LAG-3, CD223) DNA methylation correlates with LAG3 expression by tumor and immune cells, immune cell infiltration, and overall survival in clear cell renal cell carcinoma

BACKGROUND: in KIRC by methylation. METHODS: methylation in peripheral blood mononuclear cells (PBMCs) and KIRC cell lines. We validated correlations between LAG3 expression, immune cell infiltrates, survival, and methylation in an independent KIRC cohort (University Hospital Bonn (UHB) cohort, n=118) by means of immunohistochemistry and quantitative methylation-specific PCR. RESULTS: immune cell infiltrates (UHB cohort). LAG3 mRNA expression (TCGA cohort), methylation (both cohorts), and tumor cell-intrinsic protein expression (UHB cohort) was significantly associated with overall survival. CONCLUSION: DNA methylation as a predictive biomarker for response to LAG3 immune checkpoint inhibitors.