Granulocyte Colony-Stimulating Factor in Tumor Biology

Granulocyte colony-stimulating factor (G-CSF) is a cytokine best known for its role in driving the proliferation, differentiation and survival of neutrophil precursors. Within malignant tissues, however, aberrant G-CSF production by tumour or stromal cells can reshape the tumour microenvironment by mobilising granulocytic myeloid-derived suppressor cells (MDSCs), dampening cytotoxic T-cell responses, promoting angiogenesis and facilitating metastatic dissemination. Elevated G-CSF levels are increasingly recognised as both a biomarker of aggressive disease and a mechanistic contributor to chemoresistance, immune evasion and the formation of premetastatic niches. Conversely, controlled modulation of G-CSF signalling has shown promise in restoring antitumour immunity and improving responses to chemotherapy or immunotherapy. The diverse effects of G-CSF in tumour biology underscore its global significance as a double-edged sword in cancer progression and as a potential target for therapeutic intervention.

Research from Nature Portfolio

Recent studies have revealed that suppression of tumour-intrinsic pathways can limit G-CSF release and thereby restrict immunosuppressive MDSC accumulation. In a breast cancer model, stabilisation of the β-catenin destruction complex was shown to reduce G-CSF secretion by tumour-initiating cells, leading to diminished neutrophilic MDSC function and a more robust antitumour immune response. This axis highlights the therapeutic potential of targeting upstream regulators of G-CSF in malignancies characterised by high inflammatory cytokine output.

Insights into immune surveillance have further delineated how tumour-derived G-CSF subverts CD8+ T-cell–mediated clearance of disseminated cells. In syngeneic mouse models, administration of recombinant G-CSF or transfer of granulocytic MDSCs enhanced metastatic outgrowth by suppressing cytotoxic lymphocyte activity in tissues primed by nonmetastatic tumours. These findings provide molecular evidence that G-CSF–driven myeloid cells can override effective immune rejection of micro-metastases.

Granulocyte Colony-Stimulating Factor in Tumor Biology publication trend

The graph below shows the total number of articles in granulocyte colony-stimulating factor in tumor biology across all publications each year (not limited to Nature Index journals).

Technical terms

G-CSF: A cytokine that stimulates the bone marrow to produce and release neutrophils into the bloodstream.

Myeloid-derived suppressor cells (MDSCs): A heterogeneous group of immature myeloid cells that suppress T-cell responses and promote tumour progression.

Tumour microenvironment (TME): The complex milieu of immune cells, stromal cells, blood vessels and signalling molecules surrounding a tumour.

β-Catenin destruction complex: A multiprotein assembly that regulates β-catenin degradation, thereby modulating downstream gene transcription.

Signal transducer and activator of transcription 3 (STAT3): A transcription factor activated by cytokine signalling, implicated in cell survival and immunosuppression.

References

1. p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response. Nature Communications (2023).
2. Association of Granulocyte Colony-Stimulating Factor Treatment with Risk of Brain Metastasis in Advanced Stage Breast Cancer. International Journal of Molecular Sciences (2024).
3. Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism. PLOS ONE (2011).
4. G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers. Protein & Cell (2016).