Tumor mutational load and immune parameters across metastatic renal cell carcinoma risk groups

Guillermo De Velasco, Diana Miao, Martin H. Voss, A. Ari Hakimi, James J. Hsieh, Nizar M. Tannir, Pheroze Tamboli, Leonard J. Appleman, W. Kimryn Rathmell, Eliezer M. Van Allen, Toni K. Choueiri

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Non-synonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genes-granzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC.

Original languageEnglish
Pages (from-to)820-822
Number of pages3
JournalCancer immunology research
Volume4
Issue number10
DOIs
StatePublished - Oct 2016

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