title: Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.
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. 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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Guillermo
authors.initials: G
authors.lastname: de Velasco
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Diana
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Voss
authors.affiliation: Department of Surgery-Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.affiliation: Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.affiliation: Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.affiliation: Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Appleman
authors.affiliation: Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Eliezer M
authors.initials: EM
authors.lastname: Van Allen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Toni_Choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000556:secondary; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D000077594:Nivolumab; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D000077594:Nivolumab