title: Biomarkers to predict prognosis and response to checkpoint inhibitors.
abstract: Nivolumab is a fully human immunoglobulin (Ig) G4 antibody that selectively inhibits the programmed death 1 (PD-1) immune checkpoint molecule, and has recently been launched for the treatment of renal cell cancer (RCC) in Japan. Based on its promising anti-tumor efficacy and manageable safety profile demonstrated in the phase III Checkmate 025 trial, nivolumab therapy is rapidly being introduced in metastatic RCC clinical practice. The phase Ia study of atezolizumab, which is a humanized anti-PD-ligand 1 (PD-L1) monoclonal IgG1 antibody, also demonstrated excellent treatment results. The identification of biomarkers to predict the response and side-effects of checkpoint inhibitor therapy is thus urgently needed. In this review, we introduce the current candidate biomarkers of immune checkpoint inhibitor therapy. Based on the mechanism of efficacy, the number of neoantigens and expression of major histocompatibility complex molecules are strong candidate biomarkers. Despite the various interference factors, PD-L1 expression can be considered a potential biomarker. In terms of clinical factors, serum clinical factors and severity of adverse events are examined. Although further implementation in prospective studies is necessary, if validated, these biomarkers can be utilized to measure therapeutic response and design treatment strategies for metastatic RCC.
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, 135-8550, Japan. takeshi.yuasa@jfcr.or.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, 135-8550, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Masuda
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, 135-8550, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, 135-8550, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Numao
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, 135-8550, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yonese
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005805:Genes, MHC Class I / Q000276:immunology; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000077594:Nivolumab; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D000077594:Nivolumab
keywords: Adverse events; Biomarker; IMDC score; MSKCC score; Neoantigen; Nivolumab