New insights into the inflamed tumor immune microenvironment of gastric cancer with lymphoid stroma: from morphology and digital analysis to gene expression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Gullo, I (Autor) FMUP; Oliveira, P (Autor) Outra; Athelogou, M (Autor) Outra; Goncalves, G (Autor) Outra; Pinto, ML (Autor) Outra; Carvalho, J (Autor) Outra; Valente, A (Autor) Outra; Pinheiro, H (Autor) Outra; Andrade, S (Autor) Outra; Almeida, GM (Autor) Outra; Huss, R (Autor) Outra; Das, K (Autor) Outra; Tan, P (Autor) Outra; Machado JC (Autor) FMUP; Oliveira C (Autor) FMUP; Carneiro F (Autor) FMUP

Revista

Título: Gastric Cancer

Vol. 22

Páginas: 77-90

ISSN: 1436-3291

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 26 Citações

Scopus - 26 Citações

Outras Informações

ID Authenticus: P-00Q-30R

DOI: 10.1007/s10120-018-0836-8

Abstract (EN): BackgroundGastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment.MethodsTwenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations. CD3+ and CD8+ T-cell densities were calculated by digital analysis. Fifty-four non-GCLSs were used as control group.ResultsGCLSs displayed distinctive clinicopathological features, such as lower pTNM stage (p=0.02) and better overall survival (p=0.01). EBV+ or MSI-high phenotype was found in 66.7 and 16.7% cases, respectively. GCLSs harbored a cytotoxic T-cell-inflamed profile, particularly at the invasive front of tumors (p<0.01) and in EBV+ cases (p=0.01). EBV+ GCLSs, when compared to EBV- GCLSs, showed higher mRNA expression of genes related to Th1/cytotoxic and immunosuppressive biomarkers. PD-L1 protein expression, observed in neoplastic and immune stromal cells (33.3 and 91.7%, respectively), and PD-L1 amplification (18.8%) were restricted to EBV+/MSI-high tumors and correlated with high values of PD-L1 mRNA expression.ConclusionsThis study shows that GCLS has a distinctive clinico-pathological and molecular profile. Furthermore, through an in-depth study of tumor immune microenvironmentby digital analysis and mRNA expression profilingit highlights the role of EBV infection in promoting an inflamed tumor microenvironment, with putative therapeutic implications.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14