{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGranulocyte–macrophage colony‐stimulating factor (CSF2/GM‐CSF) is a key cytokine governing myeloid cell development and innate immune function. It fosters the differentiation, survival, and activation of neutrophils, monocytes, dendritic cells, and alveolar macrophages, in part by delaying neutrophil apoptosis through stabilization of anti‐apoptotic molecules via PI3K/Akt and MAPK pathways. These properties enable GM‐CSF to orchestrate rapid responses against pathogens and drive protective inflammatory reactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the tumor microenvironment, GM‐CSF is often produced by cancer cells to subvert host immunity. For example, in pancreatic ductal adenocarcinoma, tumor‐derived GM‐CSF induces the accumulation of immunosuppressive Gr‐1(+)CD11b(+) myeloid cells that restrain antigen‐specific T‐cell responses, thereby promoting tumor development. In breast cancer, mesenchymal‐like cells release GM‐CSF to activate macrophages into a tumor‐associated phenotype and trigger a positive feedback loop that enhances epithelial–mesenchymal transition and metastasis. Similar protumorigenic actions have been observed in the context of obesity‐associated metastasis and other epithelial cancers, reflecting GM‐CSF’s dual capacity to modulate inflammation and support cancer cell growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant GM‐CSF activity is also implicated in diverse autoimmune and inflammatory disorders. Neutralizing autoantibodies against GM‐CSF are central to the pathogenesis of pulmonary alveolar proteinosis by blocking its role in surfactant clearance, while excessive GM‐CSF production has been linked to severe cytokine storms in COVID‐19 and contributes to inflammatory tissue damage in conditions such as Crohn’s disease, rheumatoid arthritis, and spondyloarthritis. Additionally, GM‐CSF modulates eosinophil survival and influences actin remodelling in neutrophils, and altered GM‐CSF expression has been observed in myeloproliferative neoplasms – together underscoring its involvement in pathological inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunomodulatory roles, GM‐CSF exerts important non‐immune functions. It is secreted by airway epithelial cells to sustain neutrophil activity under infectious conditions, enhances early embryonic development by promoting blastocyst formation and increasing inner cell mass viability, and can modulate mesenchymal cell differentiation during tissue repair by influencing myofibroblast formation. 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