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NOBEL PRIZE 2026

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NIHNATIONAL CANCER INSTITUTER01

A deubiquitination module controls Treg adaptation to tumor microenvironment

Active
Institution
NORTHWESTERN UNIVERSITY AT CHICAGO, IL
Principal investigator
Deyu Fang
Funding
$560K
Duration
2021–2026
Open portfolio

Moonbase score

Still being scored

Abstract

Project Summary: One of the recent advances in cancer treatment is the development of immunotherapy largely through targeting the checkpoint receptors. However, attempts at immunotherapy to increase antitumor immune responses have achieved very limited success. A major hurdle in tumor immunotherapy is mediated by regulatory T (Treg) cells, which suppress the function of antitumor effector T cells. The lineage transcription factor Forkhead Box P3 (FoxP3) is known as a programmer for Treg adaptation in the harsh tumor microenvironment such as metabolic changes and hypoxia. However, the factors that control FoxP3-mediated Treg fitness to orchestrate the survival and functions of intratumoral Treg cells have not been identified. Importantly, our recent publications and preliminary discoveries in the current application suggest that tumor microenvironment factors possibly induce Treg fitness/adaptation through selectively upregulating a deubiquitinase module, including USP21 and USP22, but not USP7, of FoxP3 to control Treg adaptation. The current proposed studies will identify the tumor microenvironment factors that induce USP21 and USP22 expression in Tregs (Aim 1), and to test whether Tregs with simultaneous USP21 and USP22 deletion fail to adapt in the harsh tumor microenvironment, which consequently potentiates the antitumor immune therapy (Aim 2). Results from our proposed study will define a novel molecular cue in control Treg fitness to the tumor microenvironment and provide a rationale for the combined USP21 and USP22 suppression in antitumor immune therapy.

Research team

  • Deyu FangPI
  • Bin ZhangPI

LOADING MOONBASE SCORE

R01NATIONAL CANCER INSTITUTETransplantation, Tolerance, and Tumor Immunology Study Section[TTT]antitumormicroenvironmentharshtumor microenvironmenttregtreg cellsfitnessantitumor immune

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