# Understanding the cellular and functional changes in the immune tumor microenvironment of glioblastoma during progression and treatments.

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $618,825

## Abstract

Project Summary
Glioblastoma (GBM) is an incurable primary malignant brain cancer characterized by a high degree of
interpatient and intratumoral genomic and cellular heterogeneity, a brief median survival (~15 months), and
absence of an effective treatment. Even the successes of checkpoint blockade immunotherapies observed in
many cancers have not translated to GBM. The GBM tumor immune microenvironment (TIME) is highly
immunosuppressive and is dominated by resident and infiltrating myeloid cells (30-40% of the tumor mass)
compared to rare T cells (<5%). Although recent single-cell RNA-sequencing (scRNAseq) studies have
provided broad characterization of the cellular makeup and evolution of GBM tumor cells, dissecting the
diversity, function and regional localization of the immune composition of GBM remains incomplete. There is
also a widespread lack of knowledge on the evolution of intratumoral immune cells during GBM progression,
and throughout treatment with standard of care (SOC) therapies (ionizing radiation/
temozolomide/dexamethasone IR/TMZ/DEX). Major challenges to achieving scientific and clinical impact in
GBM remain, including an in-depth understanding of the interactions between cancer cells and the immune
microenvironment in the context of SOC and immunotherapy treatments. Such knowledge is difficult to obtain
using freshly excised patient samples. The main hypothesis of the proposal is that critical and clinically relevant
changes in GBM neoplastic and immune cells brought about by treatment modalities can be revealed using
genetically accurate mouse models to parse and redirect analyses of human patient datasets. A mechanistic
understanding of the effects of therapies on immune and tumorigenic cell population dynamics in pre-clinical
mouse models in combination with analysis of human patient datasets will yield transformative advancements
in the field. We will leverage archival patient samples, mouse models of GBM and GLASS consortium datasets
to uncover SOC-related cellular and molecular evolutionary changes using scRNA seq and spatial
transcriptomics. We will also unveil factors determining sensitivity and resistance to checkpoint blockade
therapy. By integrating detailed mouse and human data, we will identify areas of unrecognized therapeutic
vulnerabilities and pave the way for the development of new treatment approaches.

## Key facts

- **NIH application ID:** 10829440
- **Project number:** 5R01CA271601-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** VASSILIKI A BOUSSIOTIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,825
- **Award type:** 5
- **Project period:** 2023-04-17 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829440

## Citation

> US National Institutes of Health, RePORTER application 10829440, Understanding the cellular and functional changes in the immune tumor microenvironment of glioblastoma during progression and treatments. (5R01CA271601-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829440. Licensed CC0.

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