# A deubiquitination module controls Treg adaptation to tumor microenvironment

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $553,526

## 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.

## Key facts

- **NIH application ID:** 10320965
- **Project number:** 5R01CA257520-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Deyu Fang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $553,526
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320965

## Citation

> US National Institutes of Health, RePORTER application 10320965, A deubiquitination module controls Treg adaptation to tumor microenvironment (5R01CA257520-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320965. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*