# Comparative analysis of M-CSF and GM-CSF in human monocyte metabolic reprogramming and differentiation into tumor-associated macrophage-like cells

> **NIH NIH F30** · JOHNS HOPKINS UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY
A major component of the tumor microenvironment, tumor-associated macrophages (TAMs) play a critical role
in the orchestration of immunosuppression, cancer cell proliferation, angiogenesis, and metastasis, as well as in
resistance to cancer therapies. As the bulk of TAMs in established tumors arise from circulating monocytes,
targeting this differentiation process represents an attractive therapeutic strategy. Notably, the cytokines
macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-
CSF) are both associated with TAM differentiation. Nonetheless, M-CSF and GM-CSF can also have distinct
functional effects as they stimulate different receptors and downstream signaling pathways. In recent years,
studies in the emerging field of immunometabolism have demonstrated that changes in intracellular metabolism
downstream of cytokine activation can actively regulate immune cell differentiation and function. Despite all this,
the differences in TAM-associated functions induced by M-CSF and GM-CSF in differentiated cells and whether
early differential metabolic changes in monocytes contribute to these functional differences remain poorly
understood. My preliminary data shows that GM-CSF derived macrophages have significantly higher expression
of the TAM markers CD206 and PD-L1 than M-CSF derived macrophages, and that these differences and others
are already conspicuous in monocytes after only 7 hours of cytokine stimulation. Interestingly, my preliminary
data also shows that GM-CSF, but not M-CSF, results in a transient 7-hour period of prominent glycolytic
oscillations in monocytes. Together, these results indicate that M-CSF and GM-CSF can produce unique effects
on monocyte metabolism and TAM marker expression in differentiated cells. Considering previous studies and
my preliminary findings, the central hypothesis of this proposal is that M-CSF and GM-CSF derived macrophages
exhibit significant differences in TAM-associated functional characteristics due to early differential metabolic
changes in monocytes. I propose to test this hypothesis through the following specific aims: Aim 1: Characterize
differences in TAM-associated functional attributes and their regulation between M-CSF and GM-CSF at early
and end points of differentiation of monocytes into TAM-like cells; Aim 2: Investigate whether differences in early
metabolic changes induced by M-CSF and GM-CSF in monocytes contribute to differences in TAM marker
expression in differentiated cells. These aims will be achieved through a combination of immunology, cancer
biology, genome-wide profiling, and cell metabolism techniques with human monocytes isolated from healthy
donor peripheral blood and differentiated in in vitro cultures to TAM-like cells. Collectively, the results of this work
will advance our understanding of important functional differences between M-CSF and GM-CSF induced TAM-
like cells and potentially reveal novel metabolic...

## Key facts

- **NIH application ID:** 10995910
- **Project number:** 1F30CA294601-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Lillian Xu
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995910

## Citation

> US National Institutes of Health, RePORTER application 10995910, Comparative analysis of M-CSF and GM-CSF in human monocyte metabolic reprogramming and differentiation into tumor-associated macrophage-like cells (1F30CA294601-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995910. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*