PD-L1+ neutrophils induced NETs in malignant ascites is a potential biomarker in HCC.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-10-03 DOI:10.1007/s00262-024-03833-z
Xiaoyu Sun, Yaoqi Gui, Tai Yang, Lingbing Chen, Yi Zhang, Ling Yan, Weixian Chen, Bo Wang
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Abstract

Background: Since differentiating malignant ascites from benign ascites has always been a clinical difficult, recognition of novel biomarkers in malignant ascites of hepatocellular carcinoma (HCC) patients could be helpful for establishing a diagnosis for HCC patients with ascitic fluids.

Methods: Thirty-five HCC patients with malignant ascites and chronic liver diseases patients with benign ascites were enrolled. Serum and ascites specimens were collected to determine TAN subpopulations and NETs concentration. Then, the correlation between ascitic NETs levels and clinical features were analyzed, and ROC curves were generated to evaluate the diagnostic value of NETs. For in vitro study, fresh neutrophils were employed to explore the underlying mechanism of TAN polarization and NETs formation using RNAseq analysis.

Results: Significantly increased pro-tumor PD-L1+ TANs and higher lactate levels were measured in HCC ascites. RNAseq data showed that lactate regulated genes expression involving PD-L1 expression and NETs formation, suggesting that ascitic lactate might be responsible for tumor progression in TME. Then, NETs-related markers including calprotectin, dsDNA, CitH3, MPO and MPO-DNA were found dramatically elevated in malignant ascites. Next, correlation analysis revealed that ascitic NETs levels positively correlated with LDH, a classic ascitic biochemical indicator. Furthermore, we identified the diagnostic values of NETs in discriminating malignant ascites from benign ascites.

Conclusions: Our findings highlighted that elevated ascitic NETs served as a biomarker in HCC patients with malignant ascites, which provided useful insights for both clinical and basic research for malignant ascites diagnosis and management.

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恶性腹水中PD-L1+中性粒细胞诱导的NET是HCC的潜在生物标志物。
背景:由于恶性腹水与良性腹水的鉴别一直是临床难题,因此识别肝细胞癌(HCC)患者恶性腹水中的新型生物标志物有助于对有腹水的 HCC 患者进行确诊:方法:研究人员招募了 35 名患有恶性腹水的 HCC 患者和患有良性腹水的慢性肝病患者。收集血清和腹水标本,测定 TAN 亚群和 NETs 浓度。然后,分析腹水 NETs 水平与临床特征之间的相关性,并生成 ROC 曲线以评估 NETs 的诊断价值。体外研究采用新鲜中性粒细胞,利用RNAseq分析探讨TAN极化和NETs形成的内在机制:结果:在 HCC 腹水中测得了显著增加的亲肿瘤 PD-L1+ TAN 和较高的乳酸盐水平。RNAseq数据显示,乳酸调节涉及PD-L1表达和NETs形成的基因表达,这表明腹水乳酸可能是TME中肿瘤进展的原因。恶性腹水中的钙蛋白、dsDNA、CitH3、MPO和MPO-DNA等NETs相关标记物显著升高。接着,相关分析表明,腹水 NETs 水平与腹水生化指标 LDH 呈正相关。此外,我们还发现了 NETs 在区分恶性腹水和良性腹水方面的诊断价值:我们的研究结果表明,腹腔 NETs 升高可作为 HCC 恶性腹水患者的生物标志物,这为恶性腹水诊断和管理的临床和基础研究提供了有益的启示。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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