title: Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system.
abstract: Immune checkpoint receptors are crucial molecules for fine-tuning immune responses. Checkpoint signaling dampens T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. It is well established that tumors use several mechanisms to avoid elimination by the immune system, and one involves hijacking these checkpoint pathways. Checkpoint blockade therapy utilizes monoclonal antibodies to release the brakes from suppressed T cells, allowing them to be activated and recover their antitumor activity. This therapeutic approach has revolutionized cancer immunotherapy, and extraordinary increases in overall survival were noted, first with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) and subsequently with anti-PD-1 (programmed cell death receptor-1) in melanoma and other malignancies.
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden. Electronic address: yagopico@gmail.com.
authors.forename: Yago
authors.initials: Y
authors.lastname: Pico de Coaña
authors.affiliation: Medical Department, Bristol-Myers Squibb, Mulgrave, Australia.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines; D003131:Combined Modality Therapy; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy; D008024:Ligands; D058990:Molecular Targeted Therapy; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D011878:Radiotherapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D007166:Immunosuppressive Agents; D008024:Ligands; D061026:Programmed Cell Death 1 Receptor
keywords: CTLA-4; MDSCs; PD-1; cancer immunotherapy; checkpoint blockade