Abstract
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.
Highlights
The influence of angiogenesis on different lymphocyte populations and on the phenotype and function of these populations has been well established
An association was observed between the two pro-angiogenic monocyte populations in our study
Tie2 was expressed by 11% of monocytes and VEGFR-1 by 9% of monocytes and 5% of monocytes co-expressed VEGFR-1 and Tie2 before treatment
Summary
The influence of angiogenesis on different lymphocyte populations and on the phenotype and function of these populations has been well established. Angiopoietin 2 stimulates Tie monocytes to suppress T cell activation and promote regulatory T cell expansion via the upregulation of IL-10 and C-C motif chemokine ligand 17 (CCL17) [9], a chemokine favouring the recruitment of CCR4 positive Treg [21] In both the murine models and primary isolated human cells, a subpopulation of monocytes/macrophages expressing VEGFR-1 has been found to be highly angiogenic and to support metastasis growth [22]. Renal cell carcinoma (RCC) is one of the most vascularized tumors due to the deletion, mutation, or promoter hypermethylation of the von Hippel–Lindau gene which is common (70%) in clear-cell RCC, accounting for 75% of RCCs [25,26] These abnormalities lead to an upregulation of hypoxia-inducible factor (HIF) target genes, mainly those encoding for VEGF and angiopoietin-2, favoring angiogenesis [25,27]. The decrease in the concentrations of these populations may be associated with clinical response to antiangiogenic drugs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
