Abstract 5087: KDR mutation as novel biomarker for immune checkpoint inhibitors in pan-cancer

Abstract Purpose: Immune Checkpoint Inhibitors (ICIs) have marked important milestones in cancer treatment, while few patients experience clinical benefits from them. Therefore, reliable predictive markers for ICIs are urgently needed. Nowadays, the combination of antiangiogenic therapy and ICIs exhibits encouraging efficacy. As a key protein of VEGFR signaling, KDR may also function to regulate immune responses beyond its role in angiogenesis. Experimental Design: Pan-cancer immunotherapeutic patients from public cohorts including genomic data and clinical data were analyzed. Further analysis was performed on an internal validation data set including 67 non-small cell lung cancer (NSCLC). Investigation on underlying mechanism was performed in The Cancer Genome Atlas (TCGA) data via bioinformatics analysis. Results: We found better responses to ICIs in patients who harbored KDR mutation from pan-cancer public datasets (discovery cohort: n=662; validation cohort: n=1333). Our NSCLC cohort verified the value of KDR mutation in predicting better ICI outcomes, including objective response rate (70.0% vs 22.81%, P=0.0057) and progression-free survival (HR=0.158, 95% CI, 0.045-0.773; P=0.007). KDR mutation was associated with increased TMB level, neoantigen burden, immune cellular activities, and decreased VEGFR signaling. Meanwhile, KDR mutation was indicative of an immune-hot status, characterized by higher expression of PD-L1 and abundance of cytotoxic lymphocytes. Conclusions: Our work demonstrates that KDR mutation has the potential to become a predictive biomarker for ICIs. Citation Format: Renhua Guo, Yanan Cui, Pengpeng Zhang, Xiao Liang, Jiali Xu, Xinyin Liu, Yuemin Wu, Wei Wang, Fang Zhang, Junling Zhang, Mengli Huang. KDR mutation as novel biomarker for immune checkpoint inhibitors in pan-cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5087.