Discovery of a Biomarker That Predicts Increased Sensitivity to Immune Checkpoint Blocking Agents.

Abstract

Cancer cells undergo immune evasion through expression of PDL1, a ligand for PD1 immune checkpoint suppressor, and research has been focused on the development of a blocking agent to reduce this immune tolerance threshold. Several inhibitory antibodies for both PD1 and PDL1 have shown promising clinical responses in melanoma, non-small cell lung carcinoma and renal cell carcinoma. However, a subset of malignancies display limited efficacy to the blocking agent, even though they display PDL1 expression. Therefore we undertook this study to discover biomarkers predicting sensitivity to blocking agents that target this immune tolerance pathway. We performed in-silico analysis using TCGA dataset to identify biomarkers predicting sensitivity to inhibition of the immune tolerance pathway. We also analyzed alteration in gene expression that was seen exclusively in immune tolerance blocking agent-sensitive malignancies. Our analysis identified that PDL1 expression in itself is not a practical biomarker. However, dysregulation of cyclin-CDK network together with PDL1 expression is a potential candidate for predicting sensitivity to immune tolerance pathway inhibition.