[The "immune checkpoints", how does it work]

Clémence Granier; Vassili Soumelis; Marion Mandavit; Laure Gibault; Radia Belazzoug; Eléonore de Guillebon; Cécile Badoual; Eric Tartour; Hélène Roussel

doi:10.1016/j.annpat.2016.12.007

[The "immune checkpoints", how does it work]

Ann Pathol. 2017 Feb;37(1):18-28. doi: 10.1016/j.annpat.2016.12.007. Epub 2017 Feb 1.

[Article in French]

Authors

Clémence Granier¹, Vassili Soumelis², Marion Mandavit³, Laure Gibault⁴, Radia Belazzoug⁴, Eléonore de Guillebon⁵, Cécile Badoual⁶, Eric Tartour¹, Hélène Roussel⁷

Affiliations

¹ 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.
² Unité Inserm U932, institut Curie, 26, rue d'Ulm, 75005 Paris, France.
³ Unité Inserm U970, Paris Cardiovascular Research Center, PARCC, 56, rue Leblanc, 75015 Paris, France.
⁴ Service d'anatomie pathologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
⁵ 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.
⁶ 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.
⁷ 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.

PMID: 28160999
DOI: 10.1016/j.annpat.2016.12.007

Abstract

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.

Keywords: CTLA-4; Cancer; Immune checkpoint; Immunotherapy; Immunothérapie; PD-1; PD-L1.

MeSH terms

Antineoplastic Agents, Immunological / adverse effects
Antineoplastic Agents, Immunological / pharmacology
Antineoplastic Agents, Immunological / therapeutic use
B7-H1 Antigen / antagonists & inhibitors
B7-H1 Antigen / immunology*
CTLA-4 Antigen / antagonists & inhibitors
CTLA-4 Antigen / immunology*
Humans
Immunologic Memory
Immunologic Surveillance / drug effects
Immunologic Surveillance / immunology
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology*
Models, Immunological
Molecular Targeted Therapy
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / immunology*
Neoplasms / drug therapy
Neoplasms / immunology*
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology*
Receptors, Immunologic / antagonists & inhibitors
Receptors, Immunologic / immunology
T-Lymphocyte Subsets / immunology*

Substances

Antineoplastic Agents, Immunological
B7-H1 Antigen
CD274 protein, human
CTLA-4 Antigen
CTLA4 protein, human
Neoplasm Proteins
PDCD1 protein, human
Programmed Cell Death 1 Receptor
Receptors, Immunologic