Oct4 activates IL-17A to orchestrate M2 macrophage polarization and cervical cancer metastasis

Sep 21, 2026

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Cervical cancer remains a highly lethal malignancy, and the mechanisms linking inflammatory signals to tumor immune microenvironments are critical. This study examines whether interleukin-17A (IL-17A) promotes cervical cancer by driving M2 macrophage polarization. IL-17A levels were higher in metastatic tissues and cells, and increased M2 polarization enhanced cervical cancer cell proliferation, migration, and invasion. Mechanistically, OCT4 transcriptionally activates IL-17A and promotes malignant traits through p38 signaling, reducing tumor growth and metastasis after OCT4 knockdown.

LanguageEnglish

CategoryResearch & Report

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Pages16

Reading Time40 min

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Abstract

Background

Methods

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Introduction

Cancer Immunology, Immunotherapy (2024) 73:73 [https://doi.org/10.1007/s00262-023-03596-z](https://doi.org/10.1007/s00262-023-03596-z) Oct4 activates IL‑17A to orchestrate M2 macrophage polarization and cervical cancer metastasis Zhuoqiong Bian1 · Xiaoling Wu2 · Qing Chen2 · Qing Gao2 · Xiang Xue2 · Yidong Wang2 Received: 29 June 2023 / Accepted: 10 December 2023 © The Author(s) 2024 Abstract Background Cervical cancer is a common malignant tumor in the female. Interleukin (IL)-17A is a proinflammatory factor and exerts a vital function in inflammatory diseases and cancers. M2 macrophage has been confirmed to promote tumor development. Nevertheless, it is not yet known whether IL-17A facilitates cervical cancer development by inducing M2 macrophage polarization. Therefore, this study was conducted to investigate the regulatory effect of IL-17A on M2 macrophage polarization and the underlying mechanism in cervical cancer development. Methods RT-qPCR was utilized for testing IL-17A expression in cancer tissues and cells. Flow cytometry was applied to evaluate the M1 or M2 macrophage polarization. Cell proliferative, migratory, and invasive capabilities were measured through colony formation and transwell assays. ChIP and luciferase reporter assays were applied to determine the interaction between IL-17A and octamer-binding transcription factor 4 (OCT4) . Results IL-17A expression and concentration were high in metastatic tissues and cells of cervical cancer. IL-17A was found to facilitate M2 macrophage polarization in cervical cancer. Furthermore, IL-17A facilitated the macrophage-mediated promotion of cervical cancer cell proliferative, migratory, and invasive capabilities. Mechanistic assays manifested that Oct4 binds to and transcriptionally activated IL-17A in cervical cancer cells. Furthermore, Oct4 promoted cervical cancer cell malignant phenotype and M2 macrophage polarization by activating the p38 pathway that, in turn, upregulated IL-17A. Additionally, in vivo experiments confirmed that Oct4 knockdown reduced tumor growth and metastasis. Conclusion Oct4 triggers IL-17A to facilitate the polarization of M2 macrophages, which promotes cervical cancer cell metastasis. Keywords Cervical cancer · IL-17A · Oct4 · M2 macrophage · p38 signaling Introduction Cervical cancer is one of the most common malignant tumors in the female reproductive system [1]. With the popularization of cervical cancer screening and vaccination, the incidence rate of cervical cancer has gradually declined [2]. Nevertheless, because of the deficiency of obvious early symptoms of cervical cancer, most patients are diagnosed with advanced stage. Therefore, many women still die from * Yidong Wang [wangyidong_edu@outlook.com](wangyidong_edu@outlook.com) 1 Department of the Fifth Rheumatology, The Fifth Hospital of Xi’an City, Xi’an 710000, Shaanxi, China 2 Department of Obstetrics and Gynecology, Second Affiliated Hospital, Xi’an Jiao Tong University, 157 West Fifth Road, Xincheng District, Xi’an 710000, Shaanxi, China cervical cancer every year. At present, the main therapeutic strategies for treating cervical cancer included surgical resection, chemotherapy, and radiotherapy [3] . These methods have effectively improved the prognosis of early cervical cancer patients, but the results for late-stage patients are not satisfactory. Therefore, it is necessary to have a deeper understanding of cervical cancer pathogenesis. Tumor-associated macrophages (TAM) in the tumor microenvironment (TME) have been confirmed to play an important role in modulating tumor metastasis, angiogenesis and are closely associated with the poor prognosis [4] . TAM can be polarized into two types in accordance with environmental stimulation, namely M1 type and M2 type [5, 6]. M1 polarized macrophages mainly play a pro-inflammatory role in killing tumor cells by highly expressing CD80 and CD86 molecule while secreting elevated levels of IL-1β and TNF

FAQs

What is the main hypothesis of the study?

The study tests whether IL-17A facilitates cervical cancer development by inducing M2 macrophage polarization and explores the underlying mechanism.

How did the researchers assess M1 versus M2 macrophage polarization?

Flow cytometry was used to evaluate macrophage polarization into M1 or M2 states.

What role does OCT4 play in IL-17A regulation and metastasis?

Oct4 binds to and transcriptionally activates IL-17A, promotes cervical cancer malignant phenotype and M2 polarization via p38 signaling, and Oct4 knockdown reduces tumor growth and metastasis.

Sep 21, 2026

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