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Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression
Nature communications, 2022-01, Vol.13 (1), p.156-156, Article 156
2022
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Details

Autor(en) / Beteiligte
Titel
Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression
Ist Teil von
  • Nature communications, 2022-01, Vol.13 (1), p.156-156, Article 156
Ort / Verlag
England: Nature Publishing Group
Erscheinungsjahr
2022
Quelle
Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
Beschreibungen/Notizen
  • Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC. Multiplex immunohistochemistry shows low MHC class I (MHCI) expression and lack of CD8 T cell infiltration in PGRN-high tumors. Inhibition of PGRN abrogates autophagy-dependent MHCI degradation and restores MHCI expression on PDAC cells. Antibody-based blockade of PGRN in a PDAC mouse model remarkably decelerates tumor initiation and progression. Notably, tumors expressing LCMV-gp33 as a model antigen are sensitized to gp33-TCR transgenic T cell-mediated cytotoxicity upon PGRN blockade. Overall, our study shows a crucial function of tumor-derived PGRN in regulating immunogenicity of primary PDAC.
Sprache
Englisch
Identifikatoren
ISSN: 2041-1723
eISSN: 2041-1723
DOI: 10.1038/s41467-021-27088-9
Titel-ID: cdi_doaj_primary_oai_doaj_org_article_c9aa189db2194c2eba13f30f461a6fdd
Format
–
Schlagworte
Adenocarcinoma, Adenocarcinoma - genetics, Adenocarcinoma - immunology, Adenocarcinoma - mortality, Adenocarcinoma - therapy, Animals, Antibodies, Antibodies, Neutralizing - pharmacology, Antigen presentation, Antigens, Antigens, Viral - genetics, Antigens, Viral - immunology, Autophagy, Autophagy - drug effects, Autophagy - genetics, Autophagy - immunology, Cancer, Carcinoma, Pancreatic Ductal - genetics, Carcinoma, Pancreatic Ductal - immunology, Carcinoma, Pancreatic Ductal - mortality, Carcinoma, Pancreatic Ductal - therapy, CD8 antigen, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - pathology, Cell Line, Tumor, Cell Movement - drug effects, Cohort Studies, Cytotoxicity, Cytotoxicity, Immunologic, Deceleration, Degradation, Gene Expression, Glycoproteins - genetics, Glycoproteins - immunology, Histocompatibility Antigens Class I - genetics, Histocompatibility Antigens Class I - immunology, Humans, Immune evasion, Immunogenicity, Immunohistochemistry, Lymphocytes, Lymphocytes T, Lymphocytic choriomeningitis virus - genetics, Lymphocytic choriomeningitis virus - immunology, Macrophages, Major histocompatibility complex, Metastases, Mice, Pancreas, Pancreatic cancer, Pancreatic Neoplasms - genetics, Pancreatic Neoplasms - immunology, Pancreatic Neoplasms - mortality, Pancreatic Neoplasms - therapy, Peptide Fragments - genetics, Peptide Fragments - immunology, Progranulins - antagonists & inhibitors, Progranulins - genetics, Progranulins - immunology, Proteolysis, Survival Analysis, T cell receptors, Toxicity, Tumor Escape - genetics, Tumor Microenvironment - genetics, Tumor Microenvironment - immunology, Tumors, Viral Proteins - genetics, Viral Proteins - immunology, Xenograft Model Antitumor Assays

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