Background: Anti-PD1 agents are successfully used in therapy to treat patients with advanced melanoma. Here, we retrospectively analysed the CD73 enzyme activity in the peripheral blood of in patients with metastatic melanoma receiving nivolumab. CD73 is an ectonucleotidase able to generate adenosine from AMP. Adenosine in the tumor microenvironment is a potent immune-suppressive mediator, so that inhibition of CD73-generating enzyme or blockade of adenosine receptors is a promising therapeutic strategy to fight cancer. Materials and methods: CD73 enzyme activity was retrospectively analysed in the plasma of patients before receiving nivolumab. Levels of CD73 enzyme activity was correlated with the survival and progression-free survival of the patients analysed in this study and a multivariate analysis was performed to evaluate the prognostic value of this factor. Results: 70% of the patients analysed in this study presented detectable CD73 activity in the plasma. High basal levels of sCD73 enzyme activity in serum were significantly associated with poor overall survival and progression-free survival in melanoma patients. In multivariate analysis, levels of CD73 significantly impact on both, overall survival and progression-free survival. Interestingly, we found that low levels of CD73 in the peripheral blood determined before treatment, were significantly associated with disease control rate to nivolumab. Patients who do not respond to nivolumab therapy instead presented higher levels of CD73 enzyme activity in the blood. Conclusion: Although our results need to be confirmed and validated, they suggest that the activity of CD73 in the peripheral blood of patients with metastatic melanoma might be useful as prognostic factor and potentially as predictor of response to nivolumab treatment. We also postulate that increased levels of CD73 may contribute to affect the response of immunotherapeutic agents in cancer patients.

Soluble CD73 in the peripheral blood: a potential biomarker in patients with advanced melanoma receiving nivolumab

Silvana Morello
;
Claudia Sorrentino;Aldo Pinto;
2018

Abstract

Background: Anti-PD1 agents are successfully used in therapy to treat patients with advanced melanoma. Here, we retrospectively analysed the CD73 enzyme activity in the peripheral blood of in patients with metastatic melanoma receiving nivolumab. CD73 is an ectonucleotidase able to generate adenosine from AMP. Adenosine in the tumor microenvironment is a potent immune-suppressive mediator, so that inhibition of CD73-generating enzyme or blockade of adenosine receptors is a promising therapeutic strategy to fight cancer. Materials and methods: CD73 enzyme activity was retrospectively analysed in the plasma of patients before receiving nivolumab. Levels of CD73 enzyme activity was correlated with the survival and progression-free survival of the patients analysed in this study and a multivariate analysis was performed to evaluate the prognostic value of this factor. Results: 70% of the patients analysed in this study presented detectable CD73 activity in the plasma. High basal levels of sCD73 enzyme activity in serum were significantly associated with poor overall survival and progression-free survival in melanoma patients. In multivariate analysis, levels of CD73 significantly impact on both, overall survival and progression-free survival. Interestingly, we found that low levels of CD73 in the peripheral blood determined before treatment, were significantly associated with disease control rate to nivolumab. Patients who do not respond to nivolumab therapy instead presented higher levels of CD73 enzyme activity in the blood. Conclusion: Although our results need to be confirmed and validated, they suggest that the activity of CD73 in the peripheral blood of patients with metastatic melanoma might be useful as prognostic factor and potentially as predictor of response to nivolumab treatment. We also postulate that increased levels of CD73 may contribute to affect the response of immunotherapeutic agents in cancer patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4704502
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