Genomics

Dataset Information

0

Opposing tumor cell-intrinsic and -extrinsic roles of the IRF1 transcription factor in anti-tumor immunity


ABSTRACT: Type I interferons (IFN-I) and IFN- foster antitumor immunity by facilitating T cell responses. Paradoxically, IFNs may promote T cell exhaustion by activating immune checkpoints. The downstream regulators of these responses are incompletely understood. Herein, we describe how Interferon Regulatory Factor 1 (IRF1) orchestrates these opposing effects of IFNs. IRF1 expression in tumors blocked Toll-like receptor and IFN-I-dependent host antitumor immunity by preventing IFN stimulated gene (ISG) programs and effector programs in dendritic cells and T cells. In contrast, expression of IRF1 in the host, but not IRF3 or IFN-, was also required for antitumor immunity to wildtype and Irf1-/- tumors. Mechanistically, tumor cell IRF1 regulated major histocompatibility class I expression and bound uniquely or together with STAT1 at many ISGs, contributing to expression of immunosuppressive but not immunostimulatory ISGs. Overexpression of PD-L1 in Irf1-/- tumors only partially restored tumor growth, suggesting that the negative effects of tumor IRF1 on antitumor immunity are multifactorial. Thus, we identify tumor cell IRF1 expression as a previously unrecognized selective inhibitor of host IFN-I dependent antitumor immunity, while host IRF1 and IFN-I are critical drivers of antitumor immune responses.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE246923 | GEO | 2024/05/01

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-01-19 | PXD037759 | Pride
2023-01-12 | GSE218033 | GEO
2007-10-12 | E-GEOD-3400 | biostudies-arrayexpress
2023-05-12 | GSE203220 | GEO
2005-12-31 | GSE3400 | GEO
2023-08-15 | GSE236763 | GEO
2017-10-30 | E-MTAB-6068 | biostudies-arrayexpress
2023-01-12 | GSE216488 | GEO
2023-01-12 | GSE216486 | GEO
2012-03-09 | E-GEOD-31264 | biostudies-arrayexpress