Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy
BackgroundImmune checkpoint inhibitors (ICIs) have led to a paradigm shift in cancer therapy, improving outcomes in the treatment of various malignancies. However, not all patients benefit to the same extend from ICI. Reliable tools to predict treatment response and outcome are missing. Soluble urok...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.646883/full |
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| author | Sven H. Loosen Sven H. Loosen Joao Gorgulho Joao Gorgulho Markus S. Jördens Maximilian Schulze-Hagen Fabian Beier Mihael Vucur Anne T. Schneider Christiane Koppe Alexander Mertens Jakob N. Kather Frank Tacke Verena Keitel Tim H. Brümmendorf Christoph Roderburg Christoph Roderburg Tom Luedde |
| author_facet | Sven H. Loosen Sven H. Loosen Joao Gorgulho Joao Gorgulho Markus S. Jördens Maximilian Schulze-Hagen Fabian Beier Mihael Vucur Anne T. Schneider Christiane Koppe Alexander Mertens Jakob N. Kather Frank Tacke Verena Keitel Tim H. Brümmendorf Christoph Roderburg Christoph Roderburg Tom Luedde |
| author_sort | Sven H. Loosen |
| collection | DOAJ |
| description | BackgroundImmune checkpoint inhibitors (ICIs) have led to a paradigm shift in cancer therapy, improving outcomes in the treatment of various malignancies. However, not all patients benefit to the same extend from ICI. Reliable tools to predict treatment response and outcome are missing. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation, whose levels are prognostic in various cancers. We evaluated circulating suPAR levels as a novel predictive and prognostic biomarker in patients receiving ICI therapy for solid tumors.MethodsA total of n = 87 patients receiving ICI therapy for different solid malignancies as well as 32 healthy controls were included into this study. Serum levels of suPAR were measured by ELISA prior to and sequentially at two time points during ICI therapy.ResultsBaseline suPAR serum levels were significantly higher in solid tumor patients compared to healthy controls. Importantly, patients with low suPAR levels both before or during ICI treatment were more likely to have a favorable response to treatment at three and six months, respectively. This finding was confirmed by multivariate binary logistic regression analysis including several clinicopathological parameters. Moreover, circulating suPAR levels before and during therapy were an independent prognostic factor for overall survival (OS). As such, patients with initial suPAR levels above our ideal prognostic cut-off value (4.86 ng/ml) had a median OS of only 160 days compared to 705 days for patients with suPAR levels below this cut-off value. Finally, low baseline suPAR levels identified a subgroup of patients who experienced ICI-related side effects which in turn were associated with favorable treatment response and outcome.ConclusionOur data suggest that measurements of suPAR serum levels are a previously unknown, easily accessible tool to predict individual treatment response and outcome to ICI therapy. Circulating suPAR might therefore be implemented into stratification algorithms to identify the ideal candidates for ICI treatment. |
| first_indexed | 2024-12-17T03:11:31Z |
| format | Article |
| id | doaj.art-c0e3be5d1a344bed89728210c650e893 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T03:11:31Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c0e3be5d1a344bed89728210c650e8932022-12-21T22:05:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.646883646883Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor TherapySven H. Loosen0Sven H. Loosen1Joao Gorgulho2Joao Gorgulho3Markus S. Jördens4Maximilian Schulze-Hagen5Fabian Beier6Mihael Vucur7Anne T. Schneider8Christiane Koppe9Alexander Mertens10Jakob N. Kather11Frank Tacke12Verena Keitel13Tim H. Brümmendorf14Christoph Roderburg15Christoph Roderburg16Tom Luedde17Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, GermanyDivision of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Aachen, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, GermanyDepartment of Medicine IV, University Hospital RWTH Aachen, Aachen, GermanyClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDivision of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Aachen, GermanyDivision of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Aachen, GermanyClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, GermanyDepartment of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, GermanyClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Medicine IV, University Hospital RWTH Aachen, Aachen, GermanyClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, GermanyClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, GermanyBackgroundImmune checkpoint inhibitors (ICIs) have led to a paradigm shift in cancer therapy, improving outcomes in the treatment of various malignancies. However, not all patients benefit to the same extend from ICI. Reliable tools to predict treatment response and outcome are missing. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation, whose levels are prognostic in various cancers. We evaluated circulating suPAR levels as a novel predictive and prognostic biomarker in patients receiving ICI therapy for solid tumors.MethodsA total of n = 87 patients receiving ICI therapy for different solid malignancies as well as 32 healthy controls were included into this study. Serum levels of suPAR were measured by ELISA prior to and sequentially at two time points during ICI therapy.ResultsBaseline suPAR serum levels were significantly higher in solid tumor patients compared to healthy controls. Importantly, patients with low suPAR levels both before or during ICI treatment were more likely to have a favorable response to treatment at three and six months, respectively. This finding was confirmed by multivariate binary logistic regression analysis including several clinicopathological parameters. Moreover, circulating suPAR levels before and during therapy were an independent prognostic factor for overall survival (OS). As such, patients with initial suPAR levels above our ideal prognostic cut-off value (4.86 ng/ml) had a median OS of only 160 days compared to 705 days for patients with suPAR levels below this cut-off value. Finally, low baseline suPAR levels identified a subgroup of patients who experienced ICI-related side effects which in turn were associated with favorable treatment response and outcome.ConclusionOur data suggest that measurements of suPAR serum levels are a previously unknown, easily accessible tool to predict individual treatment response and outcome to ICI therapy. Circulating suPAR might therefore be implemented into stratification algorithms to identify the ideal candidates for ICI treatment.https://www.frontiersin.org/articles/10.3389/fonc.2021.646883/fullimmunotherapycheckpoint inhibitorsprognosisbiomarkernivolumabpembrolizumab |
| spellingShingle | Sven H. Loosen Sven H. Loosen Joao Gorgulho Joao Gorgulho Markus S. Jördens Maximilian Schulze-Hagen Fabian Beier Mihael Vucur Anne T. Schneider Christiane Koppe Alexander Mertens Jakob N. Kather Frank Tacke Verena Keitel Tim H. Brümmendorf Christoph Roderburg Christoph Roderburg Tom Luedde Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy Frontiers in Oncology immunotherapy checkpoint inhibitors prognosis biomarker nivolumab pembrolizumab |
| title | Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy |
| title_full | Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy |
| title_fullStr | Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy |
| title_full_unstemmed | Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy |
| title_short | Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy |
| title_sort | serum levels of soluble urokinase plasminogen activator receptor predict tumor response and outcome to immune checkpoint inhibitor therapy |
| topic | immunotherapy checkpoint inhibitors prognosis biomarker nivolumab pembrolizumab |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.646883/full |
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