# Glut1+ cancer associated fibroblasts enforce a metabolic barrier to tumor T cell infiltration

> **NIH NIH F31** · CEDARS-SINAI MEDICAL CENTER · 2023 · $41,294

## Abstract

PROJECT SUMMARY
T cell trafficking to tumors represents a critical process in the tumor immunity cycle. However, many tumors
can recruit T cells to the tumor, but these T cells are restricted to the tumor margin and fail to infiltrate to the
inner tumor parenchyma. The resulting “immune excluded” tumors are poorly responsive to T cell targeting
immunotherapy treatments. Cancer Associated Fibroblasts (CAFs) are the major stromal cells in many tumors
and may restrict T cell infiltration by secreting dense extracellular matrix that physically blocks the movement of
lymphocytes into tumors. Recent studies in carcinomas show that CAFs are highly heterogenous in expression
profiles and their functional role in tumors. However, the role of CAFs in soft-tissue sarcoma tumors has not
been defined. Furthermore, little is known about which specific populations of CAFs are mediators of T cell
exclusion and if mechanisms other than extracellular matrix deposition contribute to the exclusion of T cells.
The proposed research project will address the hypothesis that CAFs block T cell infiltration at the tumor
margin through their altered glucose metabolism and blocking CAFs glucose metabolism may promote
cytotoxic T cell infiltration into the tumor mass. In this line, inhibiting CAF glucose metabolism in combination
with immune-based therapies may further promote a cytotoxic anti-tumor response. Using a model of immune
excluded soft-tissue sarcoma developed in our lab, we will deplete the tumors of the glucose addicted CAFs
using aSMA-TK mice. In complementary experiments, glucose metabolism of CAFs will be disrupted using
conditional deletion of the glucose transporter, GLUT1, to determine if blocking CAF glucose metabolism can
restore T cell infiltration. The combination GLUT1 inhibition and anti-PD-1 blockade will be evaluated for its
effects on tumor growth and the effects on the infiltration and activation status of the cytotoxic T cells with
respect to tumor cells and CAFs through a highly multiplexed spatial proteomics approach. These experiments
will highlight novel mechanisms of CAFs in immune exclusion and immune escape. These findings will
highlight strategies to target pro-tumor CAFs to promote immune infiltration to ultimately sensitize tumors to
immunotherapies.

## Key facts

- **NIH application ID:** 10752508
- **Project number:** 1F31CA284888-01
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Marina T Broz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $41,294
- **Award type:** 1
- **Project period:** 2024-01-19 → 2025-01-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10752508

## Citation

> US National Institutes of Health, RePORTER application 10752508, Glut1+ cancer associated fibroblasts enforce a metabolic barrier to tumor T cell infiltration (1F31CA284888-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10752508. Licensed CC0.

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