[The "immune checkpoints", how does it work].
Costimulatory molecules allow the full lymphocyte activation, whereas co-inhibitory molecules are negative counterparts that act as immune regulators, avoiding excessive response. In some context of chronic inflammation such as cancer, co-inhibitory immune checkpoint as CTLA-4, PD-1, Lag-3, Tim-3 can accumulate at the membrane of T cells leading to a state of anergy and therefore the loss of tumor growth control. Consequently, these immune checkpoints are considered as potential target in the treatment of cancer. Immunotherapy by anti-CTLA-4 and anti-PD-1/PD-L1 early demonstrated very good proof of efficacy in the setting of several cancers types, supporting the role of these molecules in tumor immune escape. The aim of this review is to summarize the pathophysiology of immune checkpoints and their therapeutic applications in cancer.
Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France; Service d'immunologie biologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Clémence
C
Granier
Unité Inserm U932, institut Curie, 26, rue d'Ulm, 75005 Paris, France.
Vassili
V
Soumelis
Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France.
Marion
M
Mandavit
Service d'anatomie pathologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Laure
L
Gibault
Service d'anatomie pathologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Radia
R
Belazzoug
Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France; Service d'oncologie médicale, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Eléonore
E
de Guillebon
Service d'anatomie pathologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France; Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France.
Cécile
C
Badoual
Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France; Service d'immunologie biologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Eric
E
Tartour
Service d'anatomie pathologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France; Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France. Electronic address: helene.roussel@aphp.fr.
Hélène
H
Roussel
D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007157:Immunologic Surveillance / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018448:Models, Immunological; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic
CTLA-4; Cancer; Immune checkpoint; Immunotherapy; Immunothérapie; PD-1; PD-L1