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Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly immune-suppressive tumor with a low response rate to single checkpoint blockade therapy. ETS homologous factor (EHF) is a tumor suppressor in PDAC. Here, we report a novel function of EHF in pancreatic cancer immune microenvironment editing and eff...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400540/ https://www.ncbi.nlm.nih.gov/pubmed/30733283 http://dx.doi.org/10.1084/jem.20180749 |
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author | Liu, Jing Jiang, Wenna Zhao, Kaili Wang, Hongwei Zhou, Tianxing Bai, Weiwei Wang, Xiuchao Zhao, Tiansuo Huang, Chongbiao Gao, Song Qin, Tai Yu, Wenwen Yang, Bo Li, Xin Fu, Danqi Tan, Wei Yang, Shengyu Ren, He Hao, Jihui |
author_facet | Liu, Jing Jiang, Wenna Zhao, Kaili Wang, Hongwei Zhou, Tianxing Bai, Weiwei Wang, Xiuchao Zhao, Tiansuo Huang, Chongbiao Gao, Song Qin, Tai Yu, Wenwen Yang, Bo Li, Xin Fu, Danqi Tan, Wei Yang, Shengyu Ren, He Hao, Jihui |
author_sort | Liu, Jing |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) is a highly immune-suppressive tumor with a low response rate to single checkpoint blockade therapy. ETS homologous factor (EHF) is a tumor suppressor in PDAC. Here, we report a novel function of EHF in pancreatic cancer immune microenvironment editing and efficacy prediction for anti-PD1 therapy. Our findings support that the deficiency of tumoral EHF induced the accumulation of regulatory T (T reg) cells and myeloid-derived suppressor cells (MDSCs) and a decrease in the number of tumor-infiltrating CD8(+) T cells. Mechanistically, EHF deficiency induced the conversion and expansion of T reg cells and MDSCs through inhibiting tumor TGFβ1 and GM-CSF secretion. EHF suppressed the transcription of TGFB1 and CSF2 by directly binding to their promoters. Mice bearing EHF overexpression tumors exhibited significantly better response to anti-PD1 therapy than those with control tumors. Our findings delineate the immunosuppressive mechanism of EHF deficiency in PDAC and highlight that EHF overexpression may improve PDAC checkpoint immunotherapy. |
format | Online Article Text |
id | pubmed-6400540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64005402019-09-04 Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma Liu, Jing Jiang, Wenna Zhao, Kaili Wang, Hongwei Zhou, Tianxing Bai, Weiwei Wang, Xiuchao Zhao, Tiansuo Huang, Chongbiao Gao, Song Qin, Tai Yu, Wenwen Yang, Bo Li, Xin Fu, Danqi Tan, Wei Yang, Shengyu Ren, He Hao, Jihui J Exp Med Research Articles Pancreatic ductal adenocarcinoma (PDAC) is a highly immune-suppressive tumor with a low response rate to single checkpoint blockade therapy. ETS homologous factor (EHF) is a tumor suppressor in PDAC. Here, we report a novel function of EHF in pancreatic cancer immune microenvironment editing and efficacy prediction for anti-PD1 therapy. Our findings support that the deficiency of tumoral EHF induced the accumulation of regulatory T (T reg) cells and myeloid-derived suppressor cells (MDSCs) and a decrease in the number of tumor-infiltrating CD8(+) T cells. Mechanistically, EHF deficiency induced the conversion and expansion of T reg cells and MDSCs through inhibiting tumor TGFβ1 and GM-CSF secretion. EHF suppressed the transcription of TGFB1 and CSF2 by directly binding to their promoters. Mice bearing EHF overexpression tumors exhibited significantly better response to anti-PD1 therapy than those with control tumors. Our findings delineate the immunosuppressive mechanism of EHF deficiency in PDAC and highlight that EHF overexpression may improve PDAC checkpoint immunotherapy. Rockefeller University Press 2019-03-04 /pmc/articles/PMC6400540/ /pubmed/30733283 http://dx.doi.org/10.1084/jem.20180749 Text en © 2019 Liu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Liu, Jing Jiang, Wenna Zhao, Kaili Wang, Hongwei Zhou, Tianxing Bai, Weiwei Wang, Xiuchao Zhao, Tiansuo Huang, Chongbiao Gao, Song Qin, Tai Yu, Wenwen Yang, Bo Li, Xin Fu, Danqi Tan, Wei Yang, Shengyu Ren, He Hao, Jihui Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma |
title | Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma |
title_full | Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma |
title_fullStr | Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma |
title_full_unstemmed | Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma |
title_short | Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma |
title_sort | tumoral ehf predicts the efficacy of anti-pd1 therapy in pancreatic ductal adenocarcinoma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400540/ https://www.ncbi.nlm.nih.gov/pubmed/30733283 http://dx.doi.org/10.1084/jem.20180749 |
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