title: Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges.
abstract: The emergence of immune 'checkpoint inhibitors' such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1) has revolutionized treatment of solid tumors including melanoma, lung cancer, among many others. The goal of checkpoint inhibitor combination therapy is to improve clinical response and minimize toxicities. Rational design of checkpoint combinations considers immune-mediated mechanisms of antitumor activity: immunogenic cell death, antigen release and presentation, activation of T-cell responses, lymphocytic infiltration into tumors and depletion of immunosuppression. Potential synergistic combinations include checkpoint blockade with conventional (radiation, chemotherapy and targeted therapies) and newer immunotherapies (cancer vaccines, oncolytic viruses, among others). Reliable biomarkers are necessary to define patients who will achieve best clinical benefit with minimal toxicity in combination therapy.
authors.affiliation: Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1079, NY 10029, USA.
authors.forename: Chrisann
authors.initials: C
authors.lastname: Kyi
authors.affiliation: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, NY 10065, USA.|Weill Cornell Medical College, 525 E 68th Street, NY 10065, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D054316:Biomarkers, Pharmacological; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: checkpoint inhibitors; combination therapies; cytotoxic T-lymphocyte antigen 4 (CTLA-4); immunotherapy; malignancy; programmed death receptor-1 (PD-1) and ligand-1 (PD-L1)