Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses
We hypothesised that the inclusion of immunosuppressive and inflammatory biomarkers in HGSOC patients would improve the sensitivity and specificity of the preoperative marker prediction of malignancy in patients with ovarian masses. We tested a panel of 29 soluble immune factors by multiplex bead im...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/3/667 |
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| author | Nirmala Chandralega Kampan Apriliana Ellya Ratna Kartikasari Cyril Deceneux Mutsa Tatenda Madondo Orla M. McNally Katie Louise Flanagan Norhaslinda A. Aziz Andrew N. Stephens John Reynolds Michael A. Quinn Magdalena Plebanski |
| author_facet | Nirmala Chandralega Kampan Apriliana Ellya Ratna Kartikasari Cyril Deceneux Mutsa Tatenda Madondo Orla M. McNally Katie Louise Flanagan Norhaslinda A. Aziz Andrew N. Stephens John Reynolds Michael A. Quinn Magdalena Plebanski |
| author_sort | Nirmala Chandralega Kampan |
| collection | DOAJ |
| description | We hypothesised that the inclusion of immunosuppressive and inflammatory biomarkers in HGSOC patients would improve the sensitivity and specificity of the preoperative marker prediction of malignancy in patients with ovarian masses. We tested a panel of 29 soluble immune factors by multiplex bead immunoassay and 16 phenotypic T cell markers by flow cytometry in pre-treatment blood samples from 66 patients undergoing surgery for suspected ovarian cancer or ovarian cancer risk reduction. The potential diagnostic utility of all parameters was explored using Volcano plots, principal component analysis (PCA) and receiver operator characteristic (ROC) analysis. We also assessed the effect of culturing PBMCs from 20 healthy donors in the presence of malignant ascites fluid. The combination of TNFR2<sup>+</sup> Tregs and IL-6 in the pre-treatment blood of patients with advanced HGSOC effectively discriminated patients with benign or malignant ovarian masses. <i>In vitro</i> culturing of the PBMCs of healthy donors in malignant ascites promoted an increase in TNFR2-expressing Tregs, which were decreased following blockade with IL-6 or STAT3 activity. Pre-treatment serum IL-6 and peripheral blood TNFR2<sup>+</sup> Tregs may be potential clinical biomarkers that can discriminate patients with malignant compared to benign ovarian cancer masses, and the relationship between IL-6 and TNFR2<sup>+</sup> Treg is likely to be mediated via the STAT3 signalling pathway. |
| first_indexed | 2024-03-11T09:50:55Z |
| format | Article |
| id | doaj.art-4f84acdfd11b4853b0dfab1d73cf154e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:50:55Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4f84acdfd11b4853b0dfab1d73cf154e2023-11-16T16:15:35ZengMDPI AGCancers2072-66942023-01-0115366710.3390/cancers15030667Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer MassesNirmala Chandralega Kampan0Apriliana Ellya Ratna Kartikasari1Cyril Deceneux2Mutsa Tatenda Madondo3Orla M. McNally4Katie Louise Flanagan5Norhaslinda A. Aziz6Andrew N. Stephens7John Reynolds8Michael A. Quinn9Magdalena Plebanski10Department of Immunology & Pathology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 6, The Alfred, Commercial Road, Melbourne, VIC 3181, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3083, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3083, AustraliaDepartment of Immunology & Pathology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 6, The Alfred, Commercial Road, Melbourne, VIC 3181, AustraliaOncology Unit, Royal Women’s Hospital, 20 Flemington Road, Parkville, VIC 3052, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3083, AustraliaDepartment of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, MalaysiaCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaBiostatistics Consulting Platform, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 6, The Alfred, Commercial Road, Melbourne, VIC 3181, AustraliaOncology Unit, Royal Women’s Hospital, 20 Flemington Road, Parkville, VIC 3052, AustraliaDepartment of Immunology & Pathology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 6, The Alfred, Commercial Road, Melbourne, VIC 3181, AustraliaWe hypothesised that the inclusion of immunosuppressive and inflammatory biomarkers in HGSOC patients would improve the sensitivity and specificity of the preoperative marker prediction of malignancy in patients with ovarian masses. We tested a panel of 29 soluble immune factors by multiplex bead immunoassay and 16 phenotypic T cell markers by flow cytometry in pre-treatment blood samples from 66 patients undergoing surgery for suspected ovarian cancer or ovarian cancer risk reduction. The potential diagnostic utility of all parameters was explored using Volcano plots, principal component analysis (PCA) and receiver operator characteristic (ROC) analysis. We also assessed the effect of culturing PBMCs from 20 healthy donors in the presence of malignant ascites fluid. The combination of TNFR2<sup>+</sup> Tregs and IL-6 in the pre-treatment blood of patients with advanced HGSOC effectively discriminated patients with benign or malignant ovarian masses. <i>In vitro</i> culturing of the PBMCs of healthy donors in malignant ascites promoted an increase in TNFR2-expressing Tregs, which were decreased following blockade with IL-6 or STAT3 activity. Pre-treatment serum IL-6 and peripheral blood TNFR2<sup>+</sup> Tregs may be potential clinical biomarkers that can discriminate patients with malignant compared to benign ovarian cancer masses, and the relationship between IL-6 and TNFR2<sup>+</sup> Treg is likely to be mediated via the STAT3 signalling pathway.https://www.mdpi.com/2072-6694/15/3/667progression-free survivalinterleukin 6high-grade serous ovarian cancerepithelial ovarian cancertumour necrosis factor 2 receptorregulatory T cells |
| spellingShingle | Nirmala Chandralega Kampan Apriliana Ellya Ratna Kartikasari Cyril Deceneux Mutsa Tatenda Madondo Orla M. McNally Katie Louise Flanagan Norhaslinda A. Aziz Andrew N. Stephens John Reynolds Michael A. Quinn Magdalena Plebanski Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses Cancers progression-free survival interleukin 6 high-grade serous ovarian cancer epithelial ovarian cancer tumour necrosis factor 2 receptor regulatory T cells |
| title | Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses |
| title_full | Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses |
| title_fullStr | Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses |
| title_full_unstemmed | Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses |
| title_short | Combining TNFR2-Expressing Tregs and IL-6 as Superior Diagnostic Biomarkers for High-Grade Serous Ovarian Cancer Masses |
| title_sort | combining tnfr2 expressing tregs and il 6 as superior diagnostic biomarkers for high grade serous ovarian cancer masses |
| topic | progression-free survival interleukin 6 high-grade serous ovarian cancer epithelial ovarian cancer tumour necrosis factor 2 receptor regulatory T cells |
| url | https://www.mdpi.com/2072-6694/15/3/667 |
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