Whole Exome Predictors Immune Checkpoint Therapy Response in Renal Cell Carcinoma

Immune checkpoint therapies, including monoclonal antibodies to programmed cell death-1 (PD-1) and cytotoxic % lymphocyte associated protein-4 (CTLA-4), yield durable clinical responses across many tumor types, including metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, predictors of response to these therapies in RCC are still unknown. Genomic characterization of large clinical cohorts of patients treated with anti-CTLA-4 and anti-PD-1 agents in melanoma and NSCLC have suggested that high mutational burden, high neoantigen burden, and high expression of certain genes in pre-treatment tumors may be associated with patient response to these therapies. In this study, we sought to investigate genomic predictors of response to anti-PD1 therapy in metastatic RCC in two independent clinical cohorts using whole exome and whole transcriptome sequencing.]]> Primary tumor tissue samples from patients who received anti-PD1 therapy for metastatic renal cell carcinoma were obtained for whole exome sequencing and whole transcriptome sequencing. DNA was extracted from formalin-fixed paraffin-embedded primary tissue as well as from whole blood for use as a normal DNA comparison. Patients who received anti-PD-1 therapy alone or in combination with anti-CTLA-4 therapy were included in the study cohort, while those who received anti-PD-1 therapy in combination with targeted therapy (e.g. everolimus, sunitinib) were excluded.]]>