Tregs in cancer immune response

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The dysfunctional immune system in common variable immunodeficiency increases the susceptibility to gastric cancer

Publication . Gullo, Irene; Costa, Catarina; Silva, Susana L.; Ferreira, Cristina; Motta, Adriana; Silva, Sara P.; Duarte Ferreira, Ruben; Rosmaninho, Pedro; Faria, Emília; Costa, José Torres da; Câmara, Rita; Gonçalves, Gilza; Santos-Antunes, João; Oliveira, Carla; Machado, José C.; Carneiro, Fátima; Sousa, Ana E.

Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p < 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.

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Entidade financiadora

Fundação para a Ciência e a Tecnologia

Programa de financiamento

9471 - RIDTI

Número da atribuição

PTDC/MED-PAT/32462/2017