# Metabolic interactions between tumor cells and the immunce system in GBM A potential Achilles heel of GBM for novel therapeutics

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $423,255

## Abstract

ABSTRACT
Background: We recently revealed that glioblastoma (GBM) contain cell populations with distinct metabolic
requirements, with fast-cycling cells (FCCs) harnessing aerobic glycolysis, and treatment-resistant slow-cycling
cells (SCCs) preferentially engaging lipid metabolism. How the different tumor cells interact with immune cells
and how this metabolic heterogeneity shapes the immune landscape in GBM has yet to be understood.
Objectives/Hypothesis: The objectives of this study are to understand the mechanisms of communication in
the tumor microenvironment, specifically to characterize the metabolic interactions between SCCs (a
therapeutically resistant population that drive disease progression and recurrence) and the immune compartment.
Here, we will investigate a model of intercellular communication within GBM where SCCs shape an
immunosuppressive tumor milieu, which in turn assume metabolic support to SCCs by providing them with lipids,
which are essential for SCC metabolism and function. Importantly, we will test multiple genetic and clinically
amenable pharmacological approaches disrupting this metabolic interplay to antagonize GBM.
Specific aims: Our specific aims will be 1) Dissect the relationship of SCCs with the tumor microenvironment,
2) Delineate how recruited immune suppressive cell mediate SCC-driven tumor progression, and 3) Establish
that immune infiltrates provide metabolic support to SCCs by providing lipids.
Study design: The link between tumor heterogeneity and tumor immune landscape in GBM will be deciphered
with specific investigations of the metabolic interplay taking place between these cellular compartments.
In aim 1, we will delineate the cell lineage (SCC vs FCC) relationship with immune infiltrates by investigating
their genomic profile and spatial organization, using single cell RNA sequencing technology and GeoMx Digital
Spatial Profiling, respectively. We will also evaluate the role of the specific adipokine, Lipocalin-2, in shaping the
immune microenvironment. In aim 2 we will employ multiple approaches disrupting the macrophage, myeloid-
derived suppressor cell, and regulatory T cell compartments, and compare the effect on survival, growth and
chemotherapy sensitivity of SCCs and FCCs. In aim 3 the use of fluorescently labeled lipids combined with flow
cytometry and time lapse imaging will enable the comparison of lipid transfer between immune cells, FCCs and
SCCs. Finally, in vivo experiments will test the hypothesis that targeting lipid trafficking (inhibition of FABP3 or
ApoE) or lipogenesis (statin treatment) provide therapeutic benefits by affecting SCCs and rendering the overall
tumor more responsive to chemotherapy. Based on the recently reported synergistic effect of statins with immune
checkpoint inhibitors, we will also evaluate the combination of statins with anti PD-1 therapy.
Impact: Successfully completed, this project will validate therapeutically amenable approaches targeting
metabolic commu...

## Key facts

- **NIH application ID:** 10522529
- **Project number:** 1R01NS121075-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Loic Pierre Deleyrolle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,255
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522529

## Citation

> US National Institutes of Health, RePORTER application 10522529, Metabolic interactions between tumor cells and the immunce system in GBM A potential Achilles heel of GBM for novel therapeutics (1R01NS121075-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522529. Licensed CC0.

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