Hyperactivity of the IL-33-ILC2s-IL-13-M-MDSCs axis promotes cervical cancer progression

Bihui Wang; Yuejie Zhu; Yulian Zhang; Zhenyu Ru; Liqiao Chen; Manli Zhang; Yufeng Wu; Jianbing Ding; Zhifang Chen

doi:10.1016/j.intimp.2024.113693

Hyperactivity of the IL-33-ILC2s-IL-13-M-MDSCs axis promotes cervical cancer progression

Int Immunopharmacol. 2024 Nov 29:144:113693. doi: 10.1016/j.intimp.2024.113693. Online ahead of print.

Authors

Bihui Wang¹, Yuejie Zhu², Yulian Zhang¹, Zhenyu Ru³, Liqiao Chen¹, Manli Zhang², Yufeng Wu¹, Jianbing Ding⁴, Zhifang Chen⁵

Affiliations

¹ Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
² Center for Reproductive Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
³ Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
⁴ Department of Immunology, College of Basic Medicine of Xinjiang Medical University, Urumqi 830054, China.
⁵ Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China. Electronic address: 645286940@qq.com.

PMID: 39615114
DOI: 10.1016/j.intimp.2024.113693

Abstract

The interleukin-33(IL-33) - group 2 innate lymphoid cells (ILC2s) - interleukin-13(IL-13) - monocytic myeloid-derived suppressor cells (M-MDSCs) axis plays a critical role in promoting immune evasion in tumors; however, its specific function in cervical cancer remains poorly understood. In this study, we observed that the proportion of IL-33-ILC2s-IL-13-M-MDSCs were significantly elevated in both cervical cancer patients and the subcutaneous U14 cervical cancer mouse model, compared to normal controls. Our results suggest that IL-33 stimulates ILC2s to secrete IL-13, which, in turn, regulates M-MDSCs to enhance their immune evasion capabilities. Notably, in vitro blockade of IL-33 and IL-13 partially restored the levels and functions of both ILC2s and M-MDSCs. In conclusion, these findings imply that the overactivation of the IL-33-ILC2s-IL-13-M-MDSCs axis may contribute to cervical cancer progression. However, further in vivo blockade studies are required to fully elucidate the precise mechanisms underlying this interaction and to assess its potential therapeutic implications for cervical cancer.

Keywords: Cervical cancer (CC); Group 2 innate lymphoid cells (ILC2s); Interleukin-13(IL-13); Interleukin-33(IL-33); Myeloid-derived suppressor cells (MDSCs).