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Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

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Title: Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels
Authors: Stephanie Baier, Max Heiduk, Marius Distler, Lena Seifert, Christoph Reissfelder, Daniela Aust, Charlotte Reiche, Ann-Christin Meinecke, Adrian M. Seifert, Jürgen Weitz, Anna Tannert, Thilo Welsch, Christoph Kahlert, Janusz von Renesse, George Miller
Source: Oncogene
Publisher Information: Springer Science and Business Media LLC, 2020.
Publication Year: 2020
Subject Terms: Adult, Male, 0301 basic medicine, Galectins, Middle Aged, Prognosis, Survival Analysis, Article, Aged [MeSH], Prognostic markers, Galectins/metabolism [MeSH], Pancreas/pathology [MeSH], Up-Regulation [MeSH], Intraepithelial Lymphocytes/metabolism [MeSH], Cohort Studies [MeSH], Neoplasm Staging [MeSH], Male [MeSH], Pancreatic Neoplasms/diagnosis [MeSH], Carcinoma, Pancreatic Ductal/diagnosis [MeSH], Pancreatic Neoplasms/mortality [MeSH], Galectins/blood [MeSH], Carcinoma, Pancreatic Ductal/blood [MeSH], Pancreatic cancer, Carcinoma, Pancreatic Ductal/immunology [MeSH], Female [MeSH], Adult [MeSH], Humans [MeSH], Intraepithelial Lymphocytes/immunology [MeSH], Carcinoma, Pancreatic Ductal/mortality [MeSH], Survival Analysis [MeSH], Middle Aged [MeSH], Pancreatic Neoplasms/immunology [MeSH], Biomarkers, Tumor/metabolism [MeSH], Biomarkers, Tumor/blood [MeSH], Prognosis [MeSH], Pancreatic Neoplasms/blood [MeSH], Pancreas/surgery [MeSH], Up-Regulation, 3. Good health, Cohort Studies, Pancreatic Neoplasms, 03 medical and health sciences, Biomarkers, Tumor, Humans, Female, Intraepithelial Lymphocytes, Pancreas, Aged, Carcinoma, Pancreatic Ductal, Neoplasm Staging
Description: 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.
Document Type: Article
Other literature type
Language: English
ISSN: 1476-5594
0950-9232
DOI: 10.1038/s41388-020-1186-7
Access URL: https://www.nature.com/articles/s41388-020-1186-7.pdf
https://pubmed.ncbi.nlm.nih.gov/32055023
http://www.nature.com/articles/s41388-020-1186-7
https://www.ncbi.nlm.nih.gov/pubmed/32055023
https://www.nature.com/articles/s41388-020-1186-7.pdf
https://pubmed.ncbi.nlm.nih.gov/32055023/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142017
https://repository.publisso.de/resource/frl:6471358
Rights: CC BY
Accession Number: edsair.doi.dedup.....1a7bf12feb6cf98febe9c7c20afdfe6c
Database: OpenAIRE
Description
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.
ISSN:14765594
09509232
DOI:10.1038/s41388-020-1186-7