Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels.

Abstract

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.

• Authors: Adrian M Seifert, Charlotte Reiche, Max Heiduk, Anna Tannert, Ann-Christin Meinecke, Stephanie Baier, Janusz von Renesse, Christoph Kahlert, Marius Distler, Thilo Welsch, Christoph Reissfelder, Daniela E Aust, George Miller, Jürgen Weitz, Lena Seifert
• Journal: Oncogene (Oncogene) Vol. 39 Issue 15 Pg. 3102-3113 (04 2020) ISSN: 1476-5594 [Electronic] England
• PMID: 32055023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Galectins
• LGALS9 protein, human

Topics

• Adult
• Aged
• Biomarkers, Tumor (blood, metabolism)
• Carcinoma, Pancreatic Ductal (blood, diagnosis, immunology, mortality)
• Cohort Studies
• Female
• Galectins (blood, metabolism)
• Humans
• Intraepithelial Lymphocytes (immunology, metabolism)
• Male
• Middle Aged
• Neoplasm Staging
• Pancreas (pathology, surgery)
• Pancreatic Neoplasms (blood, diagnosis, immunology, mortality)
• Prognosis
• Survival Analysis
• Up-Regulation