[Efficacy of PD-1/PD-L1 immune checkpoint inhibitors and PD-L1 testing in thoracic cancers].
Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1 environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1 inhibitors. In advanced NSCLC, PD1/PD-L1 inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1. PD1/PD-L1 inhibitors are currently tested in mesothelioma and thymic tumors. PD-L1 expression evaluated with immunochemistry is the most studied predictive biomarker of PD1/PD-L1 inhibitor efficacy. Tumor and immune cell expression of PD-L1 is still difficult to evaluate because of intra-tumoral heterogeneity and expression modulation by the microenvironment. Four commercial diagnostic antibodies are in development, with differences concerning recognized epitopes, methodology of evaluation of PD-L1 expression, positivity threshold, kit and platforms used. Clinical trials in NSCLC have shown that patients with tumors strongly positive for PD-L1 derived the best clinical benefit with PD1/PD-L1 inhibitors whereas clinical benefit is less common in tumors negative for PD-L1. PD-L1 expression is not a perfect biomarker since some PD-L1 negative NSCLC respond to PD1/PD-L1 inhibitors and some PD-L1 positive NSCLC do not. PD-L1 testing is likely to be implemented in daily practice for selection of advanced NSCLC that will be treated with pembrolizumab, underscoring the relevance of ongoing harmonization studies of the use of the different antibodies available for PD-L1 testing.
Unité d'oncologie thoracique, clinique de pneumologie, centre hospitalier universitaire Grenoble-Alpes, 38043 Grenoble, France.
Michaël
M
Duruisseaux
Service d'anatomie et cytologie pathologiques, pôle IUC oncopole CHU, institut universitaire du cancer de Toulouse-oncopole, 31100 Toulouse, France.
Isabelle
I
Rouquette
Département de biologie et pathologie médicales, Gustave-Roussy, 94800 Villejuif, France.
Julien
J
Adam
Service de pneumologie et oncologie thoracique, CHRU de Lille, University Lille, Siric-OncoLille, 59000 Lille, France.
Alexis
A
Cortot
Département de pathologie, hôpital Bichat, HUPNVS, Assistance publique-Hôpitaux de Paris, 75018 Paris, France.
Aurélie
A
Cazes
Service d'anatomie pathologique, hôpital européen Georges-Pompidou, 75015 Paris, France.
Laure
L
Gibault
Service de pathologie, hôpital Cochin, AP-HP, université Paris-Descartes, 75014 Paris, France.
Diane
D
Damotte
Département de biopathologie, MESOPATH, centre de lutte contre le cancer Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. Electronic address: sylvie.lantuejoul@lyon.unicancer.fr.
Sylvie
S
Lantuejoul
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy; D002986:Clinical Trials as Topic; D016903:Drug Monitoring; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy; D008654:Mesothelioma / Q000737:chemistry / Q000188:drug therapy; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D000077594:Nivolumab; D010997:Pleural Neoplasms / Q000737:chemistry / Q000188:drug therapy; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D011446:Prospective Studies; D012189:Retrospective Studies; D013899:Thoracic Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D013945:Thymoma / Q000737:chemistry / Q000188:drug therapy; D013953:Thymus Neoplasms / Q000737:chemistry / Q000188:drug therapy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C000613593:durvalumab; D000077594:Nivolumab; C000594389:atezolizumab; C582435:pembrolizumab
Cancer thoracique; Immune checkpoint; Immunohistochemistry; Immunohistochimie; PD-L1; PD-L1 testing; PD1; Réponse immune; Test PD-L1; Thoracic cancer