Cancer Lett. 2018 Feb 28;415:117-128. doi: 10.1016/j.canlet.2017.12.003. Epub 2017 Dec 6.

The role of STAT3 in leading the crosstalk between human cancers and the immune system.

Wang Y¹, Shen Y², Wang S³, Shen Q⁴, Zhou X⁵.

Author information

1: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China.
2: University of Texas Medical Branch School of Medicine, Galveston, TX 77555, USA.
3: Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Gastroenterology and Hepatology Institute, Tianjin 300070, China.
4: Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: qshen@mdanderson.org.
5: Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China. Electronic address: byron2000zhou@sina.com.

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.