Bunk, Paul, Maher, Timothy, Beyaz, Semir (May 2024) PPAR delta promotes tumor-infiltrating Treg plasticity. In: UNSPECIFIED.
Abstract
Regulatory T-cells (Tregs) accumulate within the tumor microenvironment and are exploited to suppress anti-tumor immune responses. Lipid metabolism has been implicated as a regulator of Treg function. Unexpextedly, we found the master regulator of fatty acid catabolism PPARd as a Treg-intrinsic switch that restricts tumor growth by inducing Treg plasticity. Activation of PPARd in Tregs specifically leads to inflammatory reprograming of the tumor immune microenvironment without adverse effects in the periphery. We identified PPARd-induced transcriptional, epigenetic and metabolic alterations in Tregs that drive this plasticity response. Finally, using an inducible model of PPARd gain-of-function in Tregs, we demonstrate therapeutic potential of targeting this transcription factor to enhance immunotherapy against cancer. Collectively, these results indicate that inducing Treg plasticity in tumors can be harnessed to promote anti-tumor immunity.
| Item Type: | Conference or Workshop Item (Paper) |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders |
| CSHL Authors: | |
| Communities: | CSHL labs > Beyaz lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 1 May 2024 |
| Date Deposited: | 19 Dec 2024 13:34 |
| Last Modified: | 19 Dec 2024 13:34 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41757 |
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