title: Emerging targets in cancer immunotherapy: beyond CTLA-4 and PD-1.
abstract: Manipulation of co-stimulatory or co-inhibitory checkpoint proteins allows for the reversal of tumor-induced T-cell anergy observed in cancer. The field has gained credence given success with CTLA-4 and PD-1 inhibitors. These molecules include immunoglobulin family members and the B7 subfamily as well as the TNF receptor family members. PD-L1 inhibitors and LAG-3 inhibitors have progressed through clinical trials. Other B7 family members have shown promise in preclinical models. TNFR superfamily members have shown variable success in preclinical and clinical studies. As clinical investigation in tumor immunology gains momentum, the next stage becomes learning how to combine checkpoint inhibitors and agonists with each other as well as with traditional chemotherapeutic agents.
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Amer
authors.initials: A
authors.lastname: Assal
authors.affiliation: Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Kaner
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Jacobi Medical Center, Bronx, NY 10461, USA.
authors.forename: Gopichand
authors.initials: G
authors.lastname: Pendurti
authors.affiliation: Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA.|Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human
keywords: B7 family; TNFR superfamily; checkpoint proteins; immunotherapy; translational medicine