Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing

Yushan Dong; Jingyu Chen; Yuhan Chen; Songjiang Liu

doi:10.1016/j.biopha.2023.115513

Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing

Biomed Pharmacother. 2023 Nov:167:115513. doi: 10.1016/j.biopha.2023.115513. Epub 2023 Sep 21.

Authors

Yushan Dong¹, Jingyu Chen², Yuhan Chen³, Songjiang Liu⁴

Affiliations

¹ Graduate School of Heilongjiang University of Chinese Medicine, No. 24, Heping Road, Xiangfang District, Harbin, Heilongjiang, China.
² Department of Chinese Medicine Internal Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing, China.
³ Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
⁴ The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, No.26, Heping Road, Xiangfang District, Harbin, Heilongjiang Province, China. Electronic address: liusongjiang@hljucm.net.

PMID: 37741251
DOI: 10.1016/j.biopha.2023.115513

Abstract

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.

Keywords: Cancer immunotherapy; Drug repurpose; Immunosuppression; STAT3; Tumor microenvironment.

Publication types

Review