Xiaoyu Sun, Yaoqi Gui, Tai Yang, Lingbing Chen, Yi Zhang, Ling Yan, Weixian Chen, Bo Wang
{"title":"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。","authors":"Xiaoyu Sun, Yaoqi Gui, Tai Yang, Lingbing Chen, Yi Zhang, Ling Yan, Weixian Chen, Bo Wang","doi":"10.1007/s00262-024-03833-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Significantly increased pro-tumor PD-L1<sup>+</sup> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447185/pdf/","citationCount":"0","resultStr":"{\"title\":\"PD-L1<sup>+</sup> neutrophils induced NETs in malignant ascites is a potential biomarker in HCC.\",\"authors\":\"Xiaoyu Sun, Yaoqi Gui, Tai Yang, Lingbing Chen, Yi Zhang, Ling Yan, Weixian Chen, Bo Wang\",\"doi\":\"10.1007/s00262-024-03833-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Significantly increased pro-tumor PD-L1<sup>+</sup> 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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":9595,\"journal\":{\"name\":\"Cancer Immunology, Immunotherapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447185/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Immunology, Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00262-024-03833-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-024-03833-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
PD-L1+ neutrophils induced NETs in malignant ascites is a potential biomarker in HCC.
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.
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.