Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma

Jing Liu, Wenna Jiang, Kaili Zhao, Hongwei Wang, Tianxing Zhou, Weiwei Bai, Xiuchao Wang, Tiansuo Zhao, Chongbiao Huang, Song Gao, Tai Qin, Wenwen Yu, Bo Yang, Xin Li, Danqi Fu, Wei Tan, Shengyu Yang, He Ren, Jihui Hao

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)656-673
Number of pages18
JournalJournal of Experimental Medicine
Issue number3
StatePublished - Mar 1 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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