Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

• Published in: Oncogene Vol. 39; no. 15; pp. 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-04-2020; Nature Publishing Group
• Subjects: 13/31; 13/51; 14/19; 14/63; 38; 631/67/1504/1713; 692/53/2422; Adenocarcinoma; Adult; Aged; Apoptosis; 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; Cell Biology; 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; Human Genetics; Humans; Immune checkpoint; Immune response; Internal Medicine; Intraepithelial Lymphocytes - immunology; Intraepithelial Lymphocytes - metabolism; Lectins; Lymphocytes; Lymphocytes T; Macrophages; Male; Medicine; Medicine & Public Health; Middle Aged; mRNA; Neoplasm Staging; Oncology; 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; Germany
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-020-1186-7

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.