Association of <i>KDR</i> mutation with better clinical outcomes in pan-cancer for immune checkpoint inhibitors.

Abstract

Kinase insert domain receptor (KDR) activation is associated with the immunosuppressive microenvironment. However, the efficacy of immunotherapy in patients with <i>KDR</i> mutations is still unclear. To investigate the relationship between <i>KDR</i> gene mutations and the prognosis of pan-cancer, and whether immune checkpoint inhibitors (ICIs) may improve the prognosis of patients with <i>KDR</i> mutations, we analyzed public cohorts of pan-cancer immunotherapeutic patients including genomic and clinical data.Further analysis was performed on an internal validation data set including 67 non-small cell lung cancer. Through bioinformatics analysis, potential mechanism was studied in TCGA data. We found better responses to ICIs in patients with <i>KDR</i> mutation from pan-cancer public datasets (objective response rate [ORR], 45.0% vs 25.1%, <i>P</i>=0.0058; progression-free survival [PFS], P=0.039, HR=0.586, 95% CI 0.353-0.973) and validation cohort (overall survival (OS), P=0.05, HR=0.62; 95% CI, 0.38-1.00). Our NSCLC cohort verified the value of <i>KDR</i> mutation in predicting better clinical outcomes, including ORR (70.0% vs 22.81%, P=0.0057) and PFS (HR=0.158; 95% CI, 0.045-0.773, P=0.007). <i>KDR</i> mutation was associated with tumor mutation burden high, neoantigen burden and immune cellular activities. Meanwhile, <i>KDR</i> mutation was indicative of an immune-hot status, characterized by higher expression of PD-L1 and abundance of cytotoxic lymphocytes. <i>KDR</i> mutations may be potential positive predictors for pan-cancer received ICIs.