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Oncogene ; 39(15): 3102-3113, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32055023

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a ß-galactoside-binding lectin, promotes immune suppression through T-cell inhibition, and programming of tolerogenic macrophages. Of all cancers tested, PDAC showed the highest expression of LGALS9 (galectin-9) mRNA. We analyzed formalin-fixed and paraffin-embedded specimens from 83 patients with PDAC stained for galectin-9. Using flow cytometry, we determined galectin-9 expression on immune cells from tumor and matched blood samples from 12 patients with resectable PDAC. Furthermore, we analyzed galectin-9 serum levels by enzyme-linked immunosorbent assay using serum samples from 70 patients with PDAC, from 36 individuals with benign pancreatic disease, and from 28 healthy controls. Galectin-9 was highly expressed in human PDAC compared with normal pancreas and present on both tumor and immune cells. Tumor-infiltrating immune cells, especially CD3+ T cells, showed upregulation of galectin-9 compared with immune cells from matched blood. Blood γδ T cells from PDAC patients had higher galectin-9 expression than γδ T cells from healthy individuals. Galectin-9 polarized macrophages toward a protumoral M2 phenotype leading to suppressed T-cell cytokine secretion. Furthermore, serum concentration of galectin-9 was able to discriminate PDAC from benign pancreatic disease and healthy individuals, and was prognostic for stage IV patients. Galectin-9 is a new biomarker for the detection of PDAC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/diagnóstico , Galectinas/sangue , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Estudos de Coortes , Feminino , Galectinas/metabolismo , Humanos , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pâncreas/patologia , Pâncreas/cirurgia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Prognóstico , Análise de Sobrevida , Regulação para Cima
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