title: Next generation predictive biomarkers for immune checkpoint inhibition.
abstract: With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer. Though FDA-approved indications for use of some of these novel agents depend on current protein-based programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) assays, detection methods come with several caveats. Additional predictive tools must be interrogated to discern responders from non-responders. Some of these include measurement of microsatellite instability, PD-L1 amplification, cluster of differentiation 8 (CD8) infiltrate density, and tumor mutational burden. This review serves to synthesize biomarker detection at the DNA, RNA, and protein level to more accurately forecast benefit from these novel agents.
authors.affiliation: Center for Personalized Cancer Therapy, Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Dr., La Jolla, CA, 92093, USA. ykhagi@ucsd.edu.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Khagi
authors.affiliation: Center for Personalized Cancer Therapy, Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Dr., La Jolla, CA, 92093, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Center for Personalized Cancer Therapy, Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Dr., La Jolla, CA, 92093, USA.
authors.forename: Sandip Pravin
authors.initials: SP
authors.lastname: Patel
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D014408:Biomarkers, Tumor / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor
keywords: Checkpoint inhibitor; Immunooncology; Neoantigen presentation; Predictive biomarker; Tumor microenvironment; Tumor mutational burden