Stat3-mediated Tumor Escape

STAT3 is a transcription factor that has been associated with cancer development and immunosuppression in the tumor microenvironment. Immunosurveillance and infiltration of tumors by cytotoxic cells like NK and CD8+ T cells is critical for the elimination of cancer cells, and one mechanism used by tumor cells to evade this response is the upregulation of STAT3. Phosphorylation and activation of STAT3 results in the production of immunosuppressive cytokines like IL-10 and VEGF. These cytokines dampen cytotoxic responses and can promote differentiation of Tregs, which further suppress immune activation by down-regulating expression of MHC II, CD80, and CD86 on dendritic cells (DCs). Decreased expression of antigen presenting markers on DCs results in the failure of proper stimulation of T cells.

 

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