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This combination therapy consists of the multi-kinase inhibitor regorafenib, the PD-1 checkpoint inhibitor nivolumab, and the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). Regorafenib inhibits multiple receptor tyrosine kinases involved in angiogenesis and tumor microenvironment modulation, such as VEGFR, TIE2, and PDGFR, which may sensitize tumors to immune checkpoint blockade. Nivolumab is a monoclonal antibody that blocks the Programmed cell death protein 1 (PD-1) receptor, thereby restoring T-cell mediated anti-tumor immunity. GM-CSF is added to the regimen to stimulate the recruitment, maturation, and activation of dendritic cells and other antigen-presenting cells, potentially enhancing the priming of the immune system against tumor antigens. This triplet regimen is primarily being investigated by the Affiliated Hospital of Xuzhou Medical College for the treatment of metastatic colorectal cancer, particularly in patients with microsatellite stable (MSS) disease who typically exhibit poor responses to standard immunotherapy.
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