Figure 6.

MiRNA-assisted immunotherapy. Alterations in intracellular-related signaling have four main effects on immunotherapy resistance: (A) Excessive activation of intracellular MAPK kinase pathway leads to IL-8 and VEGF production and inhibits T-lymphocyte infiltration into tumor tissue; (B) Loss of activity of the PTEN protein pathway leads to increased PI3K activity and reduced cytotoxic T-lymphocyte activity; (C) Over-activation of the Wnt signaling pathway leads to impaired or even suppressed production of MIP-1, which reduces infiltration of CD103+ dendritic cells (DCs) into tumor tissue; (D) Mutations in the JAK1/JAK2 gene promote the excessive activity of STATs family proteins and consequently the appearance of abnormal forms of IFN-γ receptors on the surface of tumor cells. MiRNAs can cause or reverse targeted therapy resistance through the mechanisms described above.