# Influence of glucose heterogeneity on the tumor immune landscape

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $132,543

## Abstract

Project Summary
Lung cancer is the leading cause of cancer-related deaths worldwide and second most common cancer in both
men and women. African American men are ~15 % more likely to develop lung cancer than their Caucasian
counterparts. Lung adenocarcinoma is the most common type of lung cancer in both smokers and never
smokers, and accounts for ~30 % of all cases. Treatment of lung cancer is moving towards drugs that specifically
target aberrant pathways involved in carcinogenesis. One such area of interest is the metabolic dysfunction,
specifically the upregulation of glucose metabolism known as the Warburg effect.. Early-stage LUAD was initially
thought to have limited glycolytic activity due to absence of low [18F] fluorodeoxyglucose (FDG) signal. However,
we reported that early LUAD are in fact glycolytically active and sequester glucose using the sodium-glucose
transporter (SGLTs), leading to the identification of a new position emission tomography tracer, methyl 4-
[18F]FDG (Me4FDG) that is transported exclusively by SGLTs. FDG is transported exclusively by GLUTs and
thus, could not be used to measure the SGLT-mediated glucose consumption of pre-malignant and early stage
LUAD. Furthermore, as the tumor progress to more advanced disease we observed spatial heterogeneity in
SGLT2 and GLUT1 expression. The molecular advantages of this switch have yet to be fully elucidated.
Our proposed work will answer basic questions regarding the cellular glucose transport efficiency of SGLT2
compared to GLUT1. We hypothesize that under conditions of low glucose availability and in early stages where
the cancer cells are in direct competition with tumor-infiltrating immune cells, SGLT2 will prove to be a more
efficient cellular transporter compared with GLUT1. We will also for the first time, investigate the impact of SGLT2
expression in shaping the tumor-immune landscape. We hypothesize the early glucose deprivation and
increased production of lactate, a metabolite produced by highly glycolytic tumors, promotes immunosuppressive
phenotypes in the tumor microenvironment. Our investigation into the metabolic competition between cancer
and tumor resident immune cells will provide meaningful insights into novel combination treatment strategies
that repairs the metabolic dysregulation, stimulates anti-tumor immune response, and eradicates LUAD in its’
early stage.

## Key facts

- **NIH application ID:** 10533689
- **Project number:** 3R01CA237401-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Claudio Scafoglio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $132,543
- **Award type:** 3
- **Project period:** 2020-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533689

## Citation

> US National Institutes of Health, RePORTER application 10533689, Influence of glucose heterogeneity on the tumor immune landscape (3R01CA237401-03S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10533689. Licensed CC0.

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