Immune Determinants of Resistance to PD-1 Blockade in Renal Cell Carcinoma

We performed an integrated bulk and single-cell transcriptomic analysis of tumors from 102 advanced renal cell carcinoma patients enrolled in a phase II clinical trial of frontline nivolumab (NCT03117309) to investigate determinants of response to anti-PD1 monotherapy. The present study includes 112 archival or pre-treatment tumors of clear cell and non-clear cell histologies from 90 patients that underwent bulk RNA sequencing (RNA-seq). For 76 patients, 74 of whom had matched RNA-seq, whole exome sequencing (WES) was also performed on tumor samples as well as matched peripheral blood. Additionally, 19 fresh tumor samples from 17 patients, including pre and post-treatment samples and mixed histologies, were locally cryopreserved and centrally processed for single cell RNA (scRNA-seq) and TCR (scTCR-seq) sequencing. 7 patients had matched scRNA/scTCRseq, RNAseq, and WES. ]]>
Inclusion Criteria:Pathologically diagnosed advanced renal cell carcinoma Consented to protocol for tissue acquisition, genomic analysis, and data deposition Met inclusion criteria for Cohort A (clear cell; Atkins, et al., 2022; PMID: 35442713) or Cohort B (non-clear cell; Atkins, et al., 2023, PMID: 36948504) or Part A of HCRN GU16-260 trial (NCT03117309)]]>