Csf2

Overview

Csf2 is the gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine that regulates hematopoiesis, myeloid cell differentiation, survival, and inflammatory activation. In biomedical literature, Csf2 is commonly discussed as an immune signaling molecule rather than as a structural protein or enzyme. Its activity is mediated through the GM-CSF receptor complex, influencing monocytes, macrophages, neutrophils, and other myeloid-lineage cells.

Functionally, Csf2 is relevant to both normal immune homeostasis and disease-associated inflammation. It has been studied in cancer immunotherapy as an adjuvant or immune-modulating component, and in inflammatory and tissue-injury settings where excessive or dysregulated GM-CSF signaling can contribute to pathology. Recent work also places Csf2 within broader cytokine networks, including pathways involving CXCL-CXCR2 signaling and neutrophil programming, as well as combination strategies with therapies such as anti-NB vaccine approaches and naxitamab in neuroblastoma.

Focus of Latest Publications

Recent publications involving Csf2 have focused primarily on its role as granulocyte-macrophage colony-stimulating factor (GM-CSF) in immunotherapy and inflammatory signaling. In cancer studies, GM-CSF was used as an immune adjuvant or engineered payload in combination approaches designed to enhance antitumor responses. One randomized phase II melanoma trial evaluated a multipeptide vaccine with or without GM-CSF and with one- or two-site administration, with the publication reporting long-term clinical outcomes from that study. Another phase II neuroblastoma trial assessed naxitamab plus stepped-up GM-CSF dosing as consolidation therapy for patients in second or later complete remission, concluding that the combination was a good option for consolidating post-relapse remission, while noting that the encouraging long-term outcome could not be attributed solely to naxitamab plus GM-CSF because of additional post-protocol therapies.

Csf2 was also studied in the context of oncolytic virus-based immunotherapy. In ovarian cancer and non-small cell lung cancer cell line models, modified oncolytic viruses were engineered to express GM-CSF or ICOSL and were combined with an EGFRxCD16 bispecific antibody to assess NK cell activation, degranulation, cytokine production, and cytotoxicity. The study found that the bispecific antibody was the main driver of NK-cell activation, while the viruses alone had limited direct impact on NK cells; however, tumor preconditioning with oncolytic viruses, especially ONCOS-102, together with the EGFRxCD16 antibody produced the strongest NK-cell cytotoxicity, including against ovarian and EGFR-mutant lung tumor cell lines.

Beyond immunotherapy, Csf2 was implicated in inflammatory lung injury. A study on radiation-induced lung injury reported that CSF2 drives the condition by eliciting PADI4-high pathogenic neutrophils, highlighting a mechanism of crosstalk between damaged epithelial cells and neutrophils in the lung microenvironment. In colorectal cancer, CSF signaling appeared within a tumor microenvironment interaction network: integrated single-cell, bulk RNA-seq, and spatial transcriptomic analyses identified an EREG/EGFR/CSF axis in EGFR inhibitor-eligible tumors, in which cancer-cell-derived EREG stimulated EGFR-expressing cancer-associated fibroblasts that then signaled via CSF to tumor-associated macrophages/monocytes, potentially promoting M2 polarization.

Key Publications

NEWJul EGFRxCD16 bispecific antibodies orchestrate superior NK cell-mediated lysis of ovarian cancer and NSCLC cell lines in combination with oncolytic viruses. (Cancer immunology, immunotherapy : CII, 2026, PMID 42397418): "...to express Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and the ligand of inducible T-cell co-stimulator (ICOSL)..."
NEWJun CSF2 drives radiation-induced lung injury by eliciting PADI4-high pathogenic neutrophils. (Journal of translational medicine, 2026, PMID 42271382): "CSF2 drives radiation-induced lung injury by eliciting PADI4-high pathogenic neutrophils."
May Risk factors for postoperative cerebrospinal fluid leak following endoscopic transsphenoidal surgery for craniopharyngioma: a multicenter cohort study with a contemporary surgeon practice survey. (Journal of neuro-oncology, 2026, PMID 42165967): "...risk factors for postoperative cerebrospinal fluid (CSF) leak following endonasal resection of craniopharyngioma..."
May Multi-Transcriptomic Analysis Reveals That EREG-Driven TME Crosstalk Defines Anti-EGFR Response in Colorectal Cancer. (Cancer medicine, 2026, PMID 42043480): "Cell interaction analysis revealed a specific "EREG/EGFR/CSF axis" in EGFRI eligible CRC: EREG derived from cancer cell stimulates EGFR-expressing non-myCAF subtypes of cancer-associated fibroblasts (CAFs), which signal via CSF to M1/M2-like Tumor-Associated Macrophages/Monocytes (TAM/TAMo), potentially promoting M2 polarization."
Jun Impact of GM-CSF and Two-Site Vaccination on Clinical Outcomes after Multipeptide Vaccination for Melanoma: Long-term Analysis of a Randomized Phase II Trial. (Clinical cancer research : an official journal of the American Association for Cancer Research, 2026, PMID 41849224): "...with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant..."
Jun A phase II trial of naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in second or later complete remission. (International journal of cancer, 2026, PMID 41670398): "We report outcome with immunotherapy using the anti-GD2 monoclonal antibody (mAb) naxitamab and granulocyte-macrophage colony-stimulating factor (GM-CSF) for consolidation of second or later CR in a phase II trial (Clinicaltrials.gov NCT01757626)."