Understanding the dual role of granulocyte-macrophage colony-stimulating factor in the lung cancer tumor microenvironment and its therapeutic implications

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that plays a complex and critical dual regulatory role in the development, progression, and immunotherapy of lung cancer. In recent years, with the deepening of research into the tumor microenvironment (TME), GM-CSF has been recognized to possess dual regulatory functions. On the one hand, GM-CSF can enhance anti-tumor immune responses by activating and recruiting immune cells. On the other hand, it may indirectly support tumor growth and immune evasion by promoting the accumulation of myeloid-derived suppressor cells (MDSCs) and tumor-associated inflammation. Consequently, the precise mechanisms and regulatory networks of GM-CSF within the lung cancer TME remain controversial, and its efficacy in different immunotherapeutic strategies requires further exploration. This review systematically summarizes the biological characteristics of GM-CSF and its expression features in lung cancer, focusing on its dual regulatory effects on immune cells within the TME, including differential modulation of tumor-associated macrophages (TAMs), MDSCs, tumor-associated neutrophils (TANs), and dendritic cells (DCs). Furthermore, this review discusses the potential application value of GM-CSF in lung cancer treatment, such as its combination with chemoradiotherapy, targeted therapy, and immune checkpoint inhibitors (ICIs) based on clinical trial evidence. Finally, we propose key directions for future research, including dissecting GM-CSF's functional determinants using single-cell multi-omics, developing biomarkers for patient stratification, and exploring novel targeted delivery systems. This review aims to provide new insights and directions for future clinical translational research and precision therapy applications of GM-CSF in lung cancer.