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FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity (ChIP-Seq)

GSE247896 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2024/04/18 Platform GPL24676
Summary
Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies, underscoring the imperative to develop strategies to counteract the tumor's ability to foster an immunologically "cold" TME. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity through bioinformatic analysis. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation, a process that redounds to the advantage of tumor cell survival.
Published in
FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity
Chen E, Wu J, Huang J et al. · Nature communications 2024 · PMID 38816360 · doi:10.1038/s41467-024-48397-9
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Direct links to NCBI, no account and no request form: the whole study as GSE247896_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1040884 and SRA study SRP472166. Searching any of these in the dataset finder brings you back here.

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