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Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression

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Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression. / Cheung, Phyllis F; Yang, JiaJin; Fang, Rui; Borgers, Arianna; Krengel, Kirsten; Stoffel, Anne; Althoff, Kristina; Yip, Chi Wai; Siu, Elaine H L; Ng, Linda W C; Lang, Karl S; Cham, Lamin B; Engel, Daniel R; Soun, Camille; Cima, Igor; Scheffler, Björn; Striefler, Jana K; Sinn, Marianne; Bahra, Marcus; Pelzer, Uwe; Oettle, Helmut; Markus, Peter; Smeets, Esther M M; Aarntzen, Erik H J G; Savvatakis, Konstantinos; Liffers, Sven-Thorsten; Lueong, Smiths S; Neander, Christian; Bazarna, Anna; Zhang, Xin; Paschen, Annette; Crawford, Howard C; Chan, Anthony W H; Cheung, Siu Tim; Siveke, Jens T.

in: NAT COMMUN, Jahrgang 13, Nr. 1, 156, 10.01.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Cheung, PF, Yang, J, Fang, R, Borgers, A, Krengel, K, Stoffel, A, Althoff, K, Yip, CW, Siu, EHL, Ng, LWC, Lang, KS, Cham, LB, Engel, DR, Soun, C, Cima, I, Scheffler, B, Striefler, JK, Sinn, M, Bahra, M, Pelzer, U, Oettle, H, Markus, P, Smeets, EMM, Aarntzen, EHJG, Savvatakis, K, Liffers, S-T, Lueong, SS, Neander, C, Bazarna, A, Zhang, X, Paschen, A, Crawford, HC, Chan, AWH, Cheung, ST & Siveke, JT 2022, 'Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression', NAT COMMUN, Jg. 13, Nr. 1, 156. https://doi.org/10.1038/s41467-021-27088-9

APA

Cheung, P. F., Yang, J., Fang, R., Borgers, A., Krengel, K., Stoffel, A., Althoff, K., Yip, C. W., Siu, E. H. L., Ng, L. W. C., Lang, K. S., Cham, L. B., Engel, D. R., Soun, C., Cima, I., Scheffler, B., Striefler, J. K., Sinn, M., Bahra, M., ... Siveke, J. T. (2022). Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression. NAT COMMUN, 13(1), [156]. https://doi.org/10.1038/s41467-021-27088-9

Vancouver

Cheung PF, Yang J, Fang R, Borgers A, Krengel K, Stoffel A et al. Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression. NAT COMMUN. 2022 Jan 10;13(1). 156. https://doi.org/10.1038/s41467-021-27088-9

Bibtex

@article{ea48d13f850449ffadc8e4b01dd825b6,
title = "Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression",
abstract = "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.",
keywords = "Adenocarcinoma/genetics, Animals, Antibodies, Neutralizing/pharmacology, Antigens, Viral/genetics, Autophagy/drug effects, CD8-Positive T-Lymphocytes/drug effects, Carcinoma, Pancreatic Ductal/genetics, Cell Line, Tumor, Cell Movement/drug effects, Cohort Studies, Cytotoxicity, Immunologic, Gene Expression, Glycoproteins/genetics, Histocompatibility Antigens Class I/genetics, Humans, Lymphocytic choriomeningitis virus/genetics, Mice, Pancreatic Neoplasms/genetics, Peptide Fragments/genetics, Progranulins/antagonists & inhibitors, Proteolysis, Survival Analysis, Tumor Escape/genetics, Tumor Microenvironment/genetics, Viral Proteins/genetics, Xenograft Model Antitumor Assays",
author = "Cheung, {Phyllis F} and JiaJin Yang and Rui Fang and Arianna Borgers and Kirsten Krengel and Anne Stoffel and Kristina Althoff and Yip, {Chi Wai} and Siu, {Elaine H L} and Ng, {Linda W C} and Lang, {Karl S} and Cham, {Lamin B} and Engel, {Daniel R} and Camille Soun and Igor Cima and Bj{\"o}rn Scheffler and Striefler, {Jana K} and Marianne Sinn and Marcus Bahra and Uwe Pelzer and Helmut Oettle and Peter Markus and Smeets, {Esther M M} and Aarntzen, {Erik H J G} and Konstantinos Savvatakis and Sven-Thorsten Liffers and Lueong, {Smiths S} and Christian Neander and Anna Bazarna and Xin Zhang and Annette Paschen and Crawford, {Howard C} and Chan, {Anthony W H} and Cheung, {Siu Tim} and Siveke, {Jens T}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = jan,
day = "10",
doi = "10.1038/s41467-021-27088-9",
language = "English",
volume = "13",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression

AU - Cheung, Phyllis F

AU - Yang, JiaJin

AU - Fang, Rui

AU - Borgers, Arianna

AU - Krengel, Kirsten

AU - Stoffel, Anne

AU - Althoff, Kristina

AU - Yip, Chi Wai

AU - Siu, Elaine H L

AU - Ng, Linda W C

AU - Lang, Karl S

AU - Cham, Lamin B

AU - Engel, Daniel R

AU - Soun, Camille

AU - Cima, Igor

AU - Scheffler, Björn

AU - Striefler, Jana K

AU - Sinn, Marianne

AU - Bahra, Marcus

AU - Pelzer, Uwe

AU - Oettle, Helmut

AU - Markus, Peter

AU - Smeets, Esther M M

AU - Aarntzen, Erik H J G

AU - Savvatakis, Konstantinos

AU - Liffers, Sven-Thorsten

AU - Lueong, Smiths S

AU - Neander, Christian

AU - Bazarna, Anna

AU - Zhang, Xin

AU - Paschen, Annette

AU - Crawford, Howard C

AU - Chan, Anthony W H

AU - Cheung, Siu Tim

AU - Siveke, Jens T

N1 - © 2022. The Author(s).

PY - 2022/1/10

Y1 - 2022/1/10

N2 - 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.

AB - 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.

KW - Adenocarcinoma/genetics

KW - Animals

KW - Antibodies, Neutralizing/pharmacology

KW - Antigens, Viral/genetics

KW - Autophagy/drug effects

KW - CD8-Positive T-Lymphocytes/drug effects

KW - Carcinoma, Pancreatic Ductal/genetics

KW - Cell Line, Tumor

KW - Cell Movement/drug effects

KW - Cohort Studies

KW - Cytotoxicity, Immunologic

KW - Gene Expression

KW - Glycoproteins/genetics

KW - Histocompatibility Antigens Class I/genetics

KW - Humans

KW - Lymphocytic choriomeningitis virus/genetics

KW - Mice

KW - Pancreatic Neoplasms/genetics

KW - Peptide Fragments/genetics

KW - Progranulins/antagonists & inhibitors

KW - Proteolysis

KW - Survival Analysis

KW - Tumor Escape/genetics

KW - Tumor Microenvironment/genetics

KW - Viral Proteins/genetics

KW - Xenograft Model Antitumor Assays

U2 - 10.1038/s41467-021-27088-9

DO - 10.1038/s41467-021-27088-9

M3 - SCORING: Journal article

C2 - 35013174

VL - 13

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 156

ER -