# Investigating the role of tumor-associated macrophages in glioblastoma multiforme

> **NIH NIH F31** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $45,520

## Abstract

Project Summary
 Glioblastoma Multiforme (GBM) is an aggressive brain tumor with a dismal 5-year survival rate of
approximately 5%. Tumor associated macrophages, including tissue resident microglia and bone marrow-
derived macrophages, comprise 10-30% of the cells in the tumor, which makes them attractive therapeutic
targets. However, preclinical studies performing TAM depletion experiments in mouse models of glioma and
GBM have yielded inconsistent results. Additionally, early clinical trials for CSF1R inhibitors, which work by
interfering with TAM survival and proliferation, have shown little efficacy despite promising preclinical studies.
One shortcoming of all of the preclinical studies that have investigated the role of TAMs in GBM is the use of
less ideal, transplantation-based GBM model systems that have only been representative of the proneural
GBM subtype. My project aims to improve upon previous studies by performing TAM depletion experiments
using highly physiologically relevant, spontaneous genetically engineered mouse models (GEMMs) of GBM
derived from two different cells of origin: subventricular zone neural stem cells (NSCs) and oligodendrocyte
progenitor cells (OPCs). Additionally, this will be the first time TAM depletion experiments are performed in
GEMMs of GBM with an NF1 deficiency, which has been suggested to have a unique role in shaping the GBM
microenvironment. TAMs have unique morphologies in the microenvironment of NSC and OPC derived GBMs,
suggesting cell of origin may influence TAM function. In addition to depletion studies, we also aim to further
characterize the TAM transcriptome in GBM by performing bulk RNAseq on TAMs isolated from spontaneous
GEMMs of GBM. As TAM transcriptomic studies performed thus far have suggested the existence of multiple
TAM populations within tumors with different functions, we plan to investigate this by performing single-cell
RNA-sequencing of TAMs in NSC and OPC derived spontaneous GBMs. Ultimately, the goal of this project is
to further decipher the role of TAMs in GBM and in doing so, reveal new therapeutic avenues to treat GBM.
 Dr. Luis Parada, with his expertise in GBM and animal disease modeling, serves as the ideal sponsor
to advise the experimental design and results interpretation throughout the proposed project. He is a
supportive and attentive mentor as well, and I am confident that my training will lay the foundation of my
success as a future independent investigator. Additionally, Gerstner Sloan Kettering will complement my
experimental training with student led journal clubs, seminars, and bi-annual retreats. Also, I am excited to
pursue my studies at Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center, a top tier,
collaborative cancer research institute that fosters an environment of people that share the goal of improving
the prognosis and treatment of cancer. Overall, my sponsor, graduate school, and research institute
environment will provide me with t...

## Key facts

- **NIH application ID:** 10067338
- **Project number:** 1F31CA247463-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Mollie E Chipman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067338

## Citation

> US National Institutes of Health, RePORTER application 10067338, Investigating the role of tumor-associated macrophages in glioblastoma multiforme (1F31CA247463-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10067338. Licensed CC0.

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