# Metabolic reprogramming of Tregs in tumor immunity

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $410,606

## Abstract

Program Description/Abstract
Metabolic reprogramming is a fundamental process underlying the growth of cancer cells and activated
lymphocytes. These rapidly dividing cells markedly upregulate aerobic glycolysis (Warburg metabolism) and
also reprogram mitochondrial oxidative phosphorylation (OXPHOS) to support the energy and growth
demands. Moreover, mTOR signaling is a central regulator of anabolic metabolism in cancer cells and
lymphocytes. While Warburg and mitochondrial metabolism and mTOR signaling are being actively studied, we
are just beginning to appreciate the involvement of other biosynthetic programs such as de novo lipid synthesis
(lipogenesis). Emerging evidence highlights that cancer immunotherapy is a powerful tool to combat cancers,
but immune tolerance mediated by immunosuppressive regulatory T cells (Tregs) represents a major obstacle
for effective anti-tumor immunity. Although mTOR was generally considered a crucial negative regulator of
Tregs, our genetic studies have revealed that mTORC1 is a pivotal positive determinant of Treg function by
linking immune signals to the lipogenic program. In our preliminary studies, disruption of the lipogenic program
in Tregs rendered the mice to reject tumor cells but did not cause obvious autoimmune disorders under steady
state. We hypothesize that lipogenic program contributes to Treg suppressive activity in the tumor
microenvironment, which could represent a novel target for cancer immunotherapy. We will test this hypothesis
by establishing the roles of Treg lipogenic programs in tumor immunity, and determining the metabolic and
signaling basis whereby lipogenesis programs Treg functions. We predict these studies will establish a new
paradigm on our understanding of lipogenic program in Tregs and how this impinges upon tumor immunity.
Insights gained from this project will likely lead to innovative strategies on cancer immunotherapy by
capitalizing on metabolic reprogramming of Tregs.

## Key facts

- **NIH application ID:** 9963155
- **Project number:** 5R01CA221290-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Hongbo Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,606
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963155

## Citation

> US National Institutes of Health, RePORTER application 9963155, Metabolic reprogramming of Tregs in tumor immunity (5R01CA221290-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9963155. Licensed CC0.

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