The role of STAT3 in leading the crosstalk between human cancers and the immune system
Abstract The development and progression of human cancers are continuously and dynamically regulated by intrinsic and extrinsic factors. As a converging point of multiple oncogenic pathways, signal transducer and activator of transcription 3 (STAT3) is constitutively activated both in tumor cells and tumor-infiltrated immune cells. Activated STAT3 persistently triggers tumor progression through direct regulation of oncogenic gene expression. Apart from its oncogenic role in regulating gene expression in tumor cells, STAT3 also paves the way for human cancer growth through immunosuppression. Activated STAT3 in immune cells results in inhibition of immune mediators and promotion of immunosuppressive factors. Therefore, STAT3 modulates the interaction between tumor cells and host immunity. Accumulating evidence suggests that targeting STAT3 may enhance anti-cancer immune responses and rescue the suppressed immunologic microenvironment in tumors. Taken together, STAT3 has emerged as a promising target in cancer immunotherapy. Highlights STAT3 is constitutively activated in both tumor cells and immune cells. Tumor progression can be triggered by STAT3 through direct regulation of oncogenes. STAT3 also mediates human cancer growth through tumor-induced immunosuppression. STAT3's dual role in both cancer and immunity renders it a promising target for cancer therapy.
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