W. Rathmell
Last active: 11/27/2019

Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.

de Velasco G, Miao D, Voss MH, Hakimi AA, Hsieh JJ, Tannir NM, Tamboli P, Appleman LJ, Rathmell WK, Van Allen EM, Choueiri TK
Cancer Immunol Res. 2016 4 (10): 820-822

PMID: 27538576 · PMCID: PMC5050137 · DOI:10.1158/2326-6066.CIR-16-0110

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. Nonsynonymous 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. Cancer Immunol Res; 4(10); 820-2. ©2016 AACR.

©2016 American Association for Cancer Research.

MeSH Terms (10)

Antibodies, Monoclonal Antineoplastic Agents Carcinoma, Renal Cell Gene Expression Regulation, Neoplastic Humans Kidney Neoplasms Mutation Nivolumab Prognosis RNA, Neoplasm

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