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 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.

Source: The Journal of Experimental Medicine - March 3, 2019 Category: Internal Medicine Authors: Liu, J., Jiang, W., Zhao, K., Wang, H., Zhou, T., Bai, W., Wang, X., Zhao, T., Huang, C., Gao, S., Qin, T., Yu, W., Yang, B., Li, X., Fu, D., Tan, W., Yang, S., Ren, H., Hao, J. Tags: Solid Tumors, Tumor Immunology Articles Source Type: research