Background: Nivolumab (nivo) is a programmed death-1 (PD-1) inhibitor that has recently been shown to increase overall survival in patients with mRCC. The association between benefit from nivo with neoantigen load, mutation load and signatures of immune infiltration has yet to be explored in mRCC. Methods: Publicly available whole exomes (WES) and whole transcriptomes (RNA-seq) from over 300 clear-cell RCC patients in the Cancer Genome Atlas (TCGA) were analyzed for mutational load, neoantigen load and expression of immune-related genes. HLA types were inferred from WES with Polysolver and neoantigens were predicted from somatic nonsynonymous mutations with NetMHCpan3.2. The same analysis pipeline was applied to paired pre-treatment germline and metastatic tumor specimens from 9 patients who received nivo for mRCC: 3 responders (CR or PR by RECIST; R) and 6 non-responders (SD or PD by RECIST; NR), all with available pre-nivo fresh biopsies of metastatic lesions. Matched RNA-seq was available on a subset of these patient samples (3 R, 3 NR). Results: Across the TCGA and nivo-treated patients cohorts, RCC had relatively few nonsynonymous mutations and neoantigens. Among the nivo-treated patients, neoantigen load was significantly higher in NR compared to R (p = 0.048), but nonsynonymous mutation load was not. An exceptional R who experienced CR (PFS > 30 months) had outlying higher expression of selected immune-related genes compared to the 8 other patient samples (p < 0.05 for PD-L1, PD-L2; p < 0.01 for CTLA4, PD-1, PRF1; p < 0.001 for GZMA, BTLA, CD8A), and was in the top 1-5% of expression of these genes among all TCGA data. Bootstrapping analysis comparing mean expression in R vs NR compared to an empirical distribution of TCGA RNA-seq data showed significantly higher expression of PD-1, PD-L1, GZMA, LAG3, IDO1, ICOS, and BTLA in R vs. NR (p < 0.05). No genes were enriched for nonsynonymous mutations in R or NR. Conclusions: This analysis suggests that both DNA- and RNA-level data may be relevant for explaining clinical benefit from nivo in mRCC. In contrast with results from other tumor types, responders to nivo did not have more mutated tumors, though immune-related gene expression may be related to response.