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  3. Tumor cells promote immunosuppression in ovarian cancer via a positive feedback loop with MDSCs through the SAA1-IL-1β axis

Tumor cells promote immunosuppression in ovarian cancer via a positive feedback loop with MDSCs through the SAA1-IL-1β axis

  • J Exp Clin Cancer Res. 2025 Sep 30;44(1):277. doi: 10.1186/s13046-025-03536-y.
Haoran Hu # 1,  Meiqin Yang # 1,  Baoyou Huang # 1 2,  Jianyi Ding 1,  Yashi Zhu 1,  Xinxin Xu 1,  Bo Yin 1,  Huijuan Zhou 1,  Tiefeng Huang 3,  Mengjie Li 3,  Yifan Kou 3,  Zilale Rahim 3,  Ang Li 4,  Wei Wang 5,  Lingfei Han 6 7
Affiliations

Affiliations

  • 1 Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
  • 2 Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
  • 3 Department of Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • 4 School of life science and technology, Tongji University, Shanghai, China. liang@tongji.edu.cn.
  • 5 Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. 2405132@tongji.edu.cn.
  • 6 Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. lingfeihan@tongji.edu.cn.
  • 7 Department of Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. lingfeihan@tongji.edu.cn.
  • # Contributed equally.
PMID: 41029721 DOI: 10.1186/s13046-025-03536-y
Abstract

Background: Immune tolerance in epithelial ovarian Cancer (EOC) enables Cancer cells to evade immune surveillance. Myeloid-derived suppressor cells (MDSCs), as crucial immunosuppressive regulators, shape the tumor microenvironment and contribute to resistance against immunotherapy. However, the regulatory mechanisms of MDSCs in ovarian Cancer remain poorly understood.

Methods: We examined the presence and distribution of MDSCs in peripheral blood and tumor tissues from EOC patients. Transcriptomic analysis was performed on ovarian Cancer cells co-cultured with MDSCs. The role of Serum Amyloid A1 (SAA1) was investigated through in vitro functional assays, co-culture experiments, and in vivo mouse models.

Results: MDSCs were enriched in both peripheral blood and tumor tissues of EOC patients. SAA1 was significantly upregulated in ovarian Cancer cells after interaction with MDSCs and confirmed in tumor samples and cell lines. Functionally, SAA1 promoted Cancer cell proliferation, migration, and invasion. It also recruited MDSCs via TLR2/4, induced the differentiation of granulocyte-monocyte progenitors (GMPs), and stimulated IL-1β secretion, which in turn enhanced SAA1 expression, forming a positive feedback loop. In vivo, SAA1 promoted tumor progression and ascites formation. Clinically, high levels of SAA1, IL-1β, and CD33⁺ MDSCs correlated with poor survival.

Conclusion: This study uncovers a novel SAA1-IL-1β feedback loop that promotes immunosuppression and progression in ovarian Cancer. These findings provide insight into tumor-immune interactions and suggest a potential biomarker and therapeutic target for EOC.

Keywords

IL-1β; Immunosuppressive microenvironment; MDSCs; SAA1; Toll-like receptor.

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