The role of granulocyte-macrophage colony-stimulating factor in head and neck cancer

Objective: To review the molecular mechanisms and biological roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) in head and neck squamous cell carcinoma, highlighting its potential clinical applications.Design: The search terms "granulocyte-macrophage colony-stimulating factor", "GM-CSF", "CSF2 '' and "head and neck squamous cell carcinoma" or "head and neck cancer" were queried in the PubMed/MEDLINE and Scopus databases.Results: Despite of being a widely expressed cytokine, the number of studies investigating the specific roles of GM-CSF in head and neck cancer was limited. Most of them investigated GM-CSF in conjunction with other cytokines. When studied alone, conflicting findings were observed in head and neck squamous cell carcinoma. GM-CSF has been shown to induce angiogenesis and local tumor invasion. Additionally, it has also been implicated in immune evasion. On the other hand, GM-CSF stimulated the differentiation of dendritic cells, which are responsible for presenting tumor antigens, and for the regulation of T cell function. Even with these paradoxical effects, there are few studies investigating the potential of GM-CSF as adjuvant therapy in head and neck cancer.Conclusion: The effects of GM-CSF in head and neck cancer may be pro- or antitumor. Understanding how one arm and not the other is activated is essential to assess the applicability and the safety of this cytokine as a therapeutic agent.