Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing

Immune effector cells in the microenvironment tend to be depleted or remodeled, unable to perform normal functions, and even promote the malignant characterization of tumors, resulting in the formation of immunosuppressive microenvironments. The strategy of reversing immunosuppressive microenvironment has been widely used to enhance the tumor immunotherapy effect. Signal transducer and activator of transcription 3 (STAT3) was found to be a crucial regulator of immunosuppressive microenvironment formation and activation as well as a factor, stimulating tumor cell proliferation, survival, invasiveness and metastasis. Therefore, regulating the immune microenvironment by targeting the STAT3 oncogenic pathway might be a new cancer therapy strategy. This review discusses the pleiotropic effects of STAT3 on immune cell populations that are critical for tumorigenesis, and introduces the novel strategies targeting STAT3 oncogenic pathway for cancer immunotherapy. Lastly, we summarize the conventional drugs used in new STAT3-targeting anti-tumor applications.