title: Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy.
abstract: With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
mesh_terms: D060890:B7-H1 Antigen / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000276:immunology*; D059447:Cell Cycle Checkpoints; D006801:Humans; D009369:Neoplasms / Q000628:therapy*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human