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The upregulation of various signaling pathways, such as the MAPK, JAK/STAT, WNT, NF-κB, and PI3K/AKT pathways, promotes the synthesis of immunosuppressive checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1), which are usually expressed by macrophages, some activated T cells and B cells (Dong and Markovic 2018)