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- W3097333495 abstract "Abstract Although immunotherapy has revolutionized cancer care, patients with pancreatic ductal adenocarcinoma (PDA) rarely respond to these treatments, a failure that is attributed to poor infiltration and activation of T cells in the tumor microenvironment (TME). We performed an in vivo CRISPR screen and identified lysine demethylase 3A (KDM3A) as a potent epigenetic regulator of immunotherapy response in PDA. Mechanistically, KDM3A acts through Krueppel-like factor 5 (KLF5) and SMAD family member 4 (SMAD4) to regulate the expression of the epidermal growth factor receptor (EGFR). Ablation of KDM3A, KLF5, SMAD4, or EGFR in tumor cells altered the immune TME and sensitized tumors to combination immunotherapy, whereas treatment of established tumors with an EGFR inhibitor, erlotinib, prompted a dose-dependent increase in intratumoral T cells. This study defines an epigenetic–transcriptional mechanism by which tumor cells modulate their immune microenvironment and highlights the potential of EGFR inhibitors as immunotherapy sensitizers in PDA. Significance: PDA remains refractory to immunotherapies. Here, we performed an in vivo CRISPR screen and identified an epigenetic–transcriptional network that regulates antitumor immunity by converging on EGFR. Pharmacologic inhibition of EGFR is sufficient to rewire the immune microenvironment. These results offer a readily accessible immunotherapy-sensitizing strategy for PDA. This article is highlighted in the In This Issue feature, p. 521" @default.
- W3097333495 created "2020-11-09" @default.
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- W3097333495 date "2021-03-01" @default.
- W3097333495 modified "2023-10-15" @default.
- W3097333495 title "Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer" @default.
- W3097333495 cites W1498931318 @default.
- W3097333495 cites W1969201526 @default.
- W3097333495 cites W1973260880 @default.
- W3097333495 cites W1979594866 @default.
- W3097333495 cites W1985445406 @default.
- W3097333495 cites W2007684630 @default.
- W3097333495 cites W2015416439 @default.
- W3097333495 cites W2018051857 @default.
- W3097333495 cites W2019214567 @default.
- W3097333495 cites W2029733458 @default.
- W3097333495 cites W2031960993 @default.
- W3097333495 cites W2039123767 @default.
- W3097333495 cites W2041986831 @default.
- W3097333495 cites W2070050178 @default.
- W3097333495 cites W2075283855 @default.
- W3097333495 cites W2076178766 @default.
- W3097333495 cites W2079597786 @default.
- W3097333495 cites W2080752012 @default.
- W3097333495 cites W2082496440 @default.
- W3097333495 cites W2083279359 @default.
- W3097333495 cites W2091884937 @default.
- W3097333495 cites W2092603991 @default.
- W3097333495 cites W2092794927 @default.
- W3097333495 cites W2097175728 @default.
- W3097333495 cites W2100122648 @default.
- W3097333495 cites W2102619694 @default.
- W3097333495 cites W2103021272 @default.
- W3097333495 cites W2103777723 @default.
- W3097333495 cites W2108234281 @default.
- W3097333495 cites W2114104545 @default.
- W3097333495 cites W2117757143 @default.
- W3097333495 cites W2123552387 @default.
- W3097333495 cites W2126177831 @default.
- W3097333495 cites W2129140055 @default.
- W3097333495 cites W2129176863 @default.
- W3097333495 cites W2130116522 @default.
- W3097333495 cites W2130350241 @default.
- W3097333495 cites W2130410032 @default.
- W3097333495 cites W2132290857 @default.
- W3097333495 cites W2133148543 @default.
- W3097333495 cites W2145063333 @default.
- W3097333495 cites W2149639441 @default.
- W3097333495 cites W2157009395 @default.
- W3097333495 cites W2158134441 @default.
- W3097333495 cites W2170551349 @default.
- W3097333495 cites W2170830174 @default.
- W3097333495 cites W2171808845 @default.
- W3097333495 cites W2201379305 @default.
- W3097333495 cites W2206971126 @default.
- W3097333495 cites W2280923709 @default.
- W3097333495 cites W2308639964 @default.
- W3097333495 cites W2345356016 @default.
- W3097333495 cites W2399999257 @default.
- W3097333495 cites W2418018584 @default.
- W3097333495 cites W2461513545 @default.
- W3097333495 cites W2555275271 @default.
- W3097333495 cites W2564351475 @default.
- W3097333495 cites W2590325921 @default.
- W3097333495 cites W2608729572 @default.
- W3097333495 cites W2622499649 @default.
- W3097333495 cites W2735132087 @default.
- W3097333495 cites W2736476343 @default.
- W3097333495 cites W2750328162 @default.
- W3097333495 cites W2765095510 @default.
- W3097333495 cites W2774267942 @default.
- W3097333495 cites W2782124401 @default.
- W3097333495 cites W2782949806 @default.
- W3097333495 cites W2783471328 @default.
- W3097333495 cites W2783722656 @default.
- W3097333495 cites W2785803176 @default.
- W3097333495 cites W2788975052 @default.
- W3097333495 cites W2790362775 @default.
- W3097333495 cites W2791483720 @default.
- W3097333495 cites W2799466853 @default.
- W3097333495 cites W2801309958 @default.
- W3097333495 cites W2809237949 @default.
- W3097333495 cites W2810919053 @default.
- W3097333495 cites W2894717949 @default.
- W3097333495 cites W2899204048 @default.