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Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor
Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor
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Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor
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Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor
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Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor
Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor
Journal Article

Plasma EV phenotype modulation in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor

2018
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Overview
Background: Plasma EVs, a heterogeneous population of vesicles with different origins, have attracted major interest as biomarker source, especially in cancer patients. Besides containing those deriving from tumour cells, the composition and phenotype of plasma EVs might reflect immune status and its modulation in relation to anti-cancer agents. Here we investigated if the EV phenotype associated with changes in routine blood tests and peripheral blood immunophenotype in metastatic renal cell cancer patients (mRCC) undergoing tyrosine kinase inhibitor (TKI) therapy. Methods: After approval by the internal ethical committee, PBMCs and plasma samples were collected from consenting patients at baseline, 3 and 6 months during therapy and stored in liquid N2 and -80°C, respectively. EVs, isolated by two-step differential centrifugation, were evaluated by flow cytometry and western blot. PBMC immunomonitoring was performed by 10-colour cytofluorimetry. Results: EVs contained in F1 (16,500 g) and F2 (118,000 g) expressed CD9 and VLA-2 and both proteins decreased in expression after 3 months TKI administration. The amount of CD9 and VLA-2 in F1 correlated significantly with a decrease of immunosuppressive CD14 +HLA-DRneg myeloid-derived suppressor cells as well as monocyte and platelet counts in samples obtained at 3 months with respect to baseline, detected by flow cytometry of PBMCs and routine blood tests. CD9 and VLA-2 in F1 EVs also correlated inversely with CD3negCD56hi16neg cells, a subset of natural killer cells. This indicates an association of circulating EV phenotype with changes occurring at peripheral blood level in RCC patients receiving TKI. Summary/Conclusion: These preliminary data suggest that plasma EVs may reflect the immune status and the immunomodulating effects occurring during cancer therapies. Additionally, they encourage the rapid development of reliable techniques for the systematic application of body fluid EVs as immune biomarkers of liquid biopsy in cancer. Funding: This work was funded by Italian Ministry of Health grant [GR2011-02351400].