Coordinated regulation of immune contexture: crosstalk between STAT3 and immune cells during breast cancer progression.

Recent insights into the molecular and cellular mechanisms underlying cancer development have revealed the tumor microenvironment (TME) immune cells to functionally affect the development and progression of breast cancer. However, insufficient evidence of TME immune modulators limit the clinical application of immunotherapy for advanced and metastatic breast cancers. Intercellular STAT3 activation of immune cells plays a central role in breast cancer TME immunosuppression and distant metastasis. Accumulating evidence suggests that targeting STAT3 and/or in combination with radiotherapy may enhance anti-cancer immune responses and rescue the systemic immunologic microenvironment in breast cancer. Indeed, apart from its oncogenic role in tumor cells, the functions of STAT3 in TME of breast cancer involve multiple types of immunosuppression and is associated with tumor cell metastasis. In this review, we summarize the available information on the functions of STAT3-related immune cells in TME of breast cancer, as well as the specific upstream and downstream targets. Additionally, we provide insights about the potential immunosuppression mechanisms of each type of evaluated immune cells. Video abstract.