RESUMO
The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1+CD14 and Tie2+CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell carcinoma (mRCC) patients were treated with two anti-angiogenic drugs, either sunitinib or pazopanib. Blood samples from 86 patients were collected prospectively at baseline (T1), and at 10 weeks (T2) and 20 weeks (T3) after starting anti-angiogenic therapy. Various subpopulations of myeloid cells (monocytes, VEGFR-1+CD14 and Tie2+CD14 cells) decreased during treatment. When patients were divided into two subgroups with a decrease (defined as a >20% reduction from baseline value) (group 1) or not (group 2) at T3 for VEGFR-1+CD14 cells, group 1 patients presented a median PFS and OS of 24 months and 37 months, respectively, compared with a median PFS of 9 months (p = 0.032) and a median OS of 16 months (p = 0.033) in group 2 patients. The reduction in Tie2+CD14 at T3 predicted a benefit in OS at 18 months after therapy (p = 0.04). In conclusion, in this prospective clinical trial, a significant decrease in subpopulations of pro-angiogenic monocytes was associated with clinical response to anti-angiogenic drugs in patients with mRCC.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/tratamento farmacológico , Monócitos/patologia , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Animais , Antígenos CD/metabolismo , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/patologia , Modelos Animais de Doenças , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Camundongos Endogâmicos BALB C , Células Mieloides/efeitos dos fármacos , Células Mieloides/patologia , Metástase Neoplásica , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Resultado do Tratamento , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Endothelial progenitor cells (EPCs) have been extensively studied for almost 19 years now and were considered as a potential marker for endothelial regeneration ability. On the other hand, circulating endothelial cells (CEC) were studied as biomarker for endothelial injury. Yet, in the literature, there is also huge incoherency in regards to terminology and protocols used. This results in misleading conclusions on the role of so called "EPCs", especially in the clinical field. The discrepancies are mainly due to strong phenotypic overlap between EPCs and circulating angiogenic cells (CAC), therefore changes in "EPC" terminology have been suggested. Other factors leading to inconsistent results are varied definitions of the studied populations and the lack of universal data reporting, which could strongly affect data interpretation. The current review is focused on controversies concerning the use of "EPCs"/CAC and CEC as putative endothelial diagnostic markers.