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Updated: Dec 26, 2025
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
c-Maf: a bad influence in the education of macrophages
Abstract:
Tumor-associated macrophages (TAMs) represent the most abundant hematopoietic cell type in the solid tumor microenvironment. TAMs drive T cell inhibition, promote angiogenesis, and produce tumor growth factors. Although they can paradoxically exert antitumor activity and prime protective immunity, the pathways driving this phenotype remain unclear. In this issue of the JCI, Liu and colleagues identified the c-Maf transcription factor as a master regulator of protumoral TAM polarization. The authors found that c-Maf promoted TAMs' immunosuppressive activity, governed their metabolic programming, and drove expression of the macrophage differentiation protein, CSF1R. Further, inhibiting c-Maf in myeloid progenitors, and consequent myeloid-lineage cells, including TAMs, delayed tumor growth. Importantly, β-glucan treatment reduced c-MAF expression in macrophages and monocytes from patients with non-small cell lung cancer (NSCLC) where c-MAF is overexpressed. These results reveal mechanisms whereby myeloid cells drive human cancer progression by thwarting protective immunity and could lead to immunotherapy for most solid malignancies.
Insights
The c-Maf transcription factor drives tumor growth by promoting immunosuppressive tumor-associated macrophages (TAMs). Inhibiting c-Maf or using β-glucan may offer new cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment.
- TAMs typically promote tumor progression, immunosuppression, and angiogenesis.
- The precise mechanisms controlling TAM polarization remain incompletely understood.
Purpose of the Study:
- To identify key regulators of protumoral TAM polarization.
- To investigate the role of the c-Maf transcription factor in TAM function.
- To explore therapeutic strategies targeting c-Maf in cancer.
Main Methods:
- Analysis of c-Maf's role in myeloid cell differentiation and function.
- Inhibition of c-Maf in myeloid progenitors and subsequent analysis of tumor growth.
- Assessment of β-glucan's effect on c-MAF expression in cancer patient cells.
Main Results:
- c-Maf was identified as a master regulator of protumoral TAM polarization.
- c-Maf promotes TAM immunosuppressive activity, metabolic programming, and CSF1R expression.
- Inhibition of c-Maf delayed tumor growth; β-glucan reduced c-MAF expression in NSCLC patient cells.
Conclusions:
- c-Maf is a critical driver of myeloid cell-mediated cancer progression.
- Targeting c-Maf presents a potential strategy for cancer immunotherapy.
- Understanding c-Maf's role may lead to treatments for various solid malignancies.
