Analysis of PD-L1 expression in non-small cell lung cancer microenvironment and its role as a potential predictive biomarker/Analise da expressao de PD-L1 no microambiente do cancer de pulmao de nao pequenas celulas e de seu papel como potencial marcador preditivo

• Published in: Revista de medicina (São Paulo, Brazil) Vol. 95; no. 2; p. 76
• Main Authors: Santos, Maria Clara Lemos, Kadekaru, Marina Yuri, de Souza, Rachel Kalkaslief, de Castro, Gilberto, Jr, Ramos, Rodrigo Nalio
• Format: Journal Article
• Language: Portuguese
• Published: Universidade de Sao Paulo. Departamento Cientifico da Faculdade de Medicina 01-04-2016
• ISSN: 0034-8554
• DOI: 10.11606/issn.1679-9836.v.95i2p76-81

Objective: To analyse the recent findings regarding programmed-death ligand 1(PD-L1) expression on tumor infiltrating immune cells in NSCLC and its potential role as a predictive biomarker for clinical outcomes and for successful PD-1/PD-L1 blocking immunotherapy. Methods: 5 databases were accessed for search: PubMed, Web of Science, Scopus, Lilacs, and Clinical Trials.gov. Articles were selected if written in English, Portuguese or Spanish and if available via institutional access. Results: 15 articles were selected. PD-L1 expression was found to be related to the presence of immature DCs and had also constitutive expression on fibroblasts derived from NSCLC specimens. PD-L1 expression in tumor infiltrating immune cells was observed to be correlated with overall survival benefit and improved tumor response after atezolizumab therapy. A significant correlation between PD-L1 expression in peripheral T cells and clinical outcomes was also detected, besides the finding of significant correlation between an increased PD-L1 expression and clinical benefits in anti-PD-1 therapy. Discussion: Preliminary observations showed that PD-L1 expression in immune cells is related to an immunosuppressive milieu in NSCLC and to clinical benefits of immunotherapy. Keywords: Immunotherapy; Carcinoma, non-small-cell lung; Antigens, CD274; Biomarkers. Objetivo: ientifica para a expressao de PD-L1 no infiltrado de celulas imunes de tumores do tipo CPCNP, alem de seu potencial uso como biomarcador preditivo de desfechos clinicos e de resposta a imunoterapia com drogas anti PD-1 e anti PD-L1. Metodos: 5 bases de dados foram consultadas para buscas (PubMed, Web of Science, Scopus, Lilacs e Clinical Trials.gov.). Artigos foram incluidos se pertinentes, disponiveis atraves de acesso institucional e se escritos em Portugues, Ingles ou Espanhol. Nao houve restricao na selecao quanto tipo de estudo ou ano de publicacao. Resultados: 15 artigos foram selecionados. Foi observado relacao entre o nivel de expressao de PD-L1 e a presenca de celulas dendriticas imaturas, alem de expressao constitutiva da molecula em fibroblastos de pacientes com CPCNP. A expressao de PD-L1 nas celulas imunes infiltradas correlacionou-se com sobrevida aumentada e resposta tumoral melhor apos terapia com atezolizumab, alem de beneficios clinicos na terapia anti-PD-1. Outros artigos demonstram correlacao significativa entre a expressao de PD-L1 em linfocitos T perifericos e desfechos clinicos. Discussao: Observacoes preliminares demonstraram que a expressao de PD-L1 nas celulas imunes estao relacionadas ao sucesso clinico da imunoterapia e ao microambiente imunossupressor visto no CPCNP. Descritores: Imunoterapia; Carcinoma pulmonar de celulas nao pequenas; Antigenos CD274; Biomarcadores.