Year: 2024
Type: conference-abstract
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.
Source: The Journal of Immunology
Authors: Paul Bunk, Timothy Maher, Semir Beyaz
Institution: Cold Spring Harbor Laboratory
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4404167422