@article{a6308a4d23b7435eb25ed5c54e69461f,
title = "Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma",
abstract = "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.",
author = "Jing Liu and Wenna Jiang and Kaili Zhao and Hongwei Wang and Tianxing Zhou and Weiwei Bai and Xiuchao Wang and Tiansuo Zhao and Chongbiao Huang and Song Gao and Tai Qin and Wenwen Yu and Bo Yang and Xin Li and Danqi Fu and Wei Tan and Shengyu Yang and He Ren and Jihui Hao",
note = "Funding Information: This work was supported by the National Natural Science Foundation of China (81525021, 81672431, 81672435, 81720108028, 81772633, 81702426, 81702427, 81572618, 81802432, 81802433, 81871968, and 81871978), the National Key Clinical Specialist Construction Programs of China (2013-544), Key Program of Prevention and Treatment of Chronic Diseases of Tianjin (17ZXMFSY0010), Key Program of Public Health Bureau Foundation of Tianjin (15KG144), the Science and Technology Development Fund of Tianjin Education Commission for Higher Education (2017KJ198), and the Foundation of Tianjin Medical University (2016KYZQ17). The research in S. Yang{\textquoteright}s laboratory is supported by the National Cancer Institute (R01 CA175741) and the Elsa U. Pardee Foundation. Funding Information: This work was supported by the National Natural Science Foundation of China (81525021, 81672431, 81672435, 81720108028, 81772633, 81702426, 81702427, 81572618, 81802432, 81802433, 81871968, and 81871978), the National Key Clinical Specialist Construction Programs of China (2013-544), Key Program of Prevention and Treatment of Chronic Diseases of Tianjin (17ZXMFSY0010), Key Program of Public Health Bureau Foundation of Tianjin (15KG144), the Science and Technology Development Fund of Tianjin Education Commission for Higher Education (2017KJ198), and the Foundation of Tianjin Medical University (2016KYZQ17). The research in S. Yang{\textquoteright}s laboratory is supported by the National Cancer Institute (R01 CA175741) and the Elsa U. Pardee Foundation. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2019 Liu et al. 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/).",
year = "2019",
month = mar,
day = "1",
doi = "10.1084/jem.20180749",
language = "English (US)",
volume = "216",
pages = "656--673",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",
}