Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a β-galactoside-binding lectin, promotes immune suppression through T-cell inhibition, and programming of tolerogenic macrophages. Of all cancers tested, PDAC showed the hig...

Full description

Saved in:
Bibliographic Details
Published in:Oncogene 2020-04, Vol.39 (15), p.3102-3113
Main Authors: Seifert, Adrian M, Reiche, Charlotte, Heiduk, Max, Tannert, Anna, Meinecke, Ann-Christin, Baier, Stephanie, von Renesse, Janusz, Kahlert, Christoph, Distler, Marius, Welsch, Thilo, Reissfelder, Christoph, Aust, Daniela E, Miller, George, Weitz, Jürgen, Seifert, Lena
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adult
Aged
Benign
Biomarkers, Tumor - blood
Biomarkers, Tumor - metabolism
Carcinoma, Pancreatic Ductal - blood
Carcinoma, Pancreatic Ductal - diagnosis
Carcinoma, Pancreatic Ductal - immunology
Carcinoma, Pancreatic Ductal - mortality
Care and treatment
CD3 antigen
Cohort Studies
CTLA-4 protein
Cytokines
Development and progression
Enzyme-linked immunosorbent assay
Female
Flow cytometry
Galectin-9
Galectins - blood
Galectins - metabolism
Gene expression
Genetic aspects
Health aspects
Humans
Immune checkpoint
Immune response
Intraepithelial Lymphocytes - immunology
Intraepithelial Lymphocytes - metabolism
Lectins
Lymphocytes
Lymphocytes T
Macrophages
Male
Middle Aged
mRNA
Neoplasm Staging
Pancreas
Pancreas - pathology
Pancreas - surgery
Pancreatic cancer
Pancreatic diseases
Pancreatic Neoplasms - blood
Pancreatic Neoplasms - diagnosis
Pancreatic Neoplasms - immunology
Pancreatic Neoplasms - mortality
Paraffin
PD-1 protein
Phenotypes
Prognosis
Regulation
Serum levels
Survival Analysis
Tumor-infiltrating lymphocytes
Up-Regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a β-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.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-020-1186-7