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Published on: February 8, 2018
Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune
Sven H Loosen1,2, Joao Gorgulho3,4, Markus S Jördens1
1Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Background:
Immune 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.
Methods:
A 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.
Results:
Baseline 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.
Conclusion:
Our 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.
Insights
Soluble urokinase plasminogen activator receptor (suPAR) can predict how well patients respond to immune checkpoint inhibitors (ICIs). Low suPAR levels indicate a better response and survival in cancer patients treated with ICIs.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but predicting patient response remains a challenge.
- Soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, shows prognostic value in various cancers.
- There is a need for reliable biomarkers to predict ICI treatment efficacy and patient outcomes.
Purpose of the Study:
- To evaluate circulating suPAR levels as a novel predictive and prognostic biomarker in patients receiving ICI therapy for solid tumors.
- To determine if suPAR levels can identify patients likely to respond favorably to ICI treatment.
- To assess the association between suPAR levels and overall survival in patients undergoing ICI therapy.
Main Methods:
- Serum suPAR levels were measured using ELISA in 87 solid tumor patients receiving ICI therapy and 32 healthy controls.
- Measurements were taken at baseline and two time points during ICI treatment.
- Multivariate binary logistic regression analysis was employed to validate findings.
Main Results:
- Solid tumor patients exhibited significantly higher baseline suPAR levels than healthy controls.
- Low suPAR levels (pre- or during ICI treatment) correlated with favorable treatment response at 3 and 6 months.
- Elevated suPAR levels (≥4.86 ng/ml) were associated with significantly shorter overall survival (160 days vs. 705 days).
- Low baseline suPAR identified patients with ICI-related side effects, who also showed favorable outcomes.
Conclusions:
- Circulating suPAR levels serve as a novel, accessible biomarker for predicting ICI treatment response and patient outcomes.
- suPAR measurements can aid in stratifying patients to identify optimal candidates for ICI therapy.
- Implementation of suPAR into clinical practice could enhance personalized cancer treatment strategies.
