NLRP3 Inflammasome Upregulates PD-L1 in Ovarian Cancer and Contributes to an Immunosuppressive Microenvironment.

IF 6.2 Q1 IMMUNOLOGY
ImmunoTargets and Therapy Pub Date : 2024-12-14 eCollection Date: 2024-01-01 DOI:10.2147/ITT.S495564
Wenjing Pan, Zhaoyang Jia, Jingtong Du, Kexin Chang, Yiming Liu, Wei Liu, Xibo Zhao, Wenhua Tan
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引用次数: 0

Abstract

Introduction: The NLRP3 inflammasome has been implicated in the initiation of inflammation and tumorigenesis; however, its role in epithelial ovarian cancer (EOC) remains unclear.

Methods: This study employed high-throughput sequencing data, ELISA, clone formation assay, Western blot, and flow cytometric analysis to investigate the specific role of the NLRP3 inflammasome in EOC.

Results: NLRP3 was highly expressed in human EOC tissues and correlated with an unfavorable prognosis. Activation of the NLRP3 inflammasome by LPS and ATP promoted EOC cell proliferation and increased IL-1 and PD-L1 levels. MCC950, a NLRP3 inflammasome blocker, reduced IL-1 and PD-L1 levels and diminished tumor-immune suppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and PD-1+ CD4+ T cells, in a murine model of ovarian cancer. This intervention also suppressed tumor growth.

Conclusion: Our investigation revealed the pro-tumorigenic role of the NLRP3 inflammasome and its regulation of PD-L1 expression in EOC. Blockade of the NLRP3 inflammasome led to reduced PD-L1 expression, fewer immunosuppressive cells, and suppressed tumor growth. These findings suggest that targeting the NLRP3 inflammasome-PD-L1 axis could be a novel treatment approach for ovarian cancer.

NLRP3炎性小体在卵巢癌中上调PD-L1并参与免疫抑制微环境
NLRP3炎性小体参与炎症的发生和肿瘤的发生;然而,其在上皮性卵巢癌(EOC)中的作用尚不清楚。方法:采用高通量测序数据、ELISA、克隆形成实验、Western blot和流式细胞术分析,探讨NLRP3炎症小体在EOC中的具体作用。结果:NLRP3在人EOC组织中高表达,与不良预后相关。LPS和ATP激活NLRP3炎性体可促进EOC细胞增殖,增加IL-1和PD-L1水平。MCC950是一种NLRP3炎性小体阻滞剂,在卵巢癌小鼠模型中降低IL-1和PD-L1水平,减少肿瘤免疫抑制细胞,如骨髓源性抑制细胞(MDSCs)、肿瘤相关巨噬细胞(tam)和PD-1+ CD4+ T细胞。这种干预也抑制了肿瘤的生长。结论:我们的研究揭示了NLRP3炎性小体在EOC中的促肿瘤作用及其对PD-L1表达的调节。阻断NLRP3炎性小体导致PD-L1表达降低,免疫抑制细胞减少,肿瘤生长受到抑制。这些发现表明,靶向NLRP3炎性体- pd - l1轴可能是卵巢癌的一种新的治疗方法。
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来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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