title: PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations.
abstract: PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota. We further clarify the mechanisms of action of these markers and their roles in shaping, being shaped, and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment.
authors.affiliation: Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA. wzou@med.umich.edu wolchokj@mskcc.org lieping.chen@yale.edu.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Medicine and the Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. wzou@med.umich.edu wolchokj@mskcc.org lieping.chen@yale.edu.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven CT 06519, USA. wzou@med.umich.edu wolchokj@mskcc.org lieping.chen@yale.edu.
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D064307:Microbiota; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D061026:Programmed Cell Death 1 Receptor