In addition, granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by tumor cells mediates the proliferation of MDSCs through the pSTAT5 pathway, and induces them to secrete pro-angiogenic proteins including IL-8 and matrix metalloproteinase-9 (MMP-9), resulting in reduced sensitivity to VEGF/VEGFR inhibitors in RCC (Figure 2A) (95). The gene discussed is MMP9; the disease is renal cell carcinoma.