Haoran Hu, Meiqin Yang, Baoyou Huang, Jianyi Ding, Yashi Zhu, Xinxin Xu, Bo Yin, Huijuan Zhou, Tiefeng Huang, Mengjie Li, Yifan Kou, Zilale Rahim, Ang Li, Wei Wang, Lingfei Han
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引用次数: 0
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.
期刊介绍:
The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications.
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