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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
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.
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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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