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Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.

ABSTRACT: Whether bevacizumab exerts its anti-tumor properties through systemic effects beyond local inhibition of angiogenesis and how these effects can be monitored in patients, remain largely elusive. To address these questions, we investigated bone marrow-derived cells and cytokines in the peripheral blood of metastatic breast cancer patients undergoing therapy with bevacizumab.Circulating endothelial cells (CEC), circulating endothelial progenitor (CEP) and circulating CD11b+ cells in metastatic breast cancer patients before and during therapy with paclitaxel alone (n = 11) or in combination with bevacizumab (n = 10) were characterized using flow cytometry, real time PCR and RNASeq. Circulating factors were measured by ELISA. Aged-matched healthy donors were used as baseline controls (n = 12).Breast cancer patients had elevated frequencies of CEC, CEP, TIE2+CD11b+ and KIT+CD11b+ cell subsets. CEC decreased during therapy, irrespective of bevacizumab, while TIE2+CD11b+ remained unchanged. KIT+CD11b+ cells decreased in response to paclitaxel with bevacizumab, but not paclitaxel alone. Cancer patients expressed higher mRNA levels of the M2 polarization markers CD163, ARG1 and IL-10 in CD11b+ cells and increased levels of the M2 cytokines IL-10 and CCL20 in plasma. M1 activation markers and cytokines were low or equally expressed in cancer patients compared to healthy donors. Chemotherapy with paclitaxel and bevacizumab, but not with paclitaxel alone, significantly decreased IL-10 mRNA in CD11b+ cells and IL-10 protein in plasma.This pilot study provides evidence of systemic immunomodulatory effects of bevacizumab and identified circulating KIT+CD11b+ cells and IL-10 as candidate biomarkers of bevacizumab activity in metastatic breast cancer patients.

SUBMITTER: Cattin S

PROVIDER: S-EPMC4905463 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.

Cattin Sarah S Fellay Benoît B Pradervand Sylvain S Trojan Andreas A Ruhstaller Thomas T Rüegg Curzio C Fürstenberger Gregor G

Oncotarget 20160301 10

<h4>Background</h4>Whether bevacizumab exerts its anti-tumor properties through systemic effects beyond local inhibition of angiogenesis and how these effects can be monitored in patients, remain largely elusive. To address these questions, we investigated bone marrow-derived cells and cytokines in the peripheral blood of metastatic breast cancer patients undergoing therapy with bevacizumab.<h4>Methods</h4>Circulating endothelial cells (CEC), circulating endothelial progenitor (CEP) and circulat ...[more]

PMID: 26840567

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Project description:BACKGROUND:Prolonged angiogenesis inhibition may improve treatment outcome in metastatic colorectal cancer (mCRC) patients. However, due to the complexity of the angiogenic pathways there is a lack of valid predictive biomarkers for anti-angiogenic agents. Here, we describe and optimize a procedure for simultaneous dynamic profiling of multiple angiogenesis related proteins in patient serum to explore associations with the response and acquired resistance to anti-angiogenic therapy. MATERIALS AND METHODS:Patients (n=22) were selected from a clinical trial investigating maintenance treatment with bevacizumab alone after response to induction chemotherapy + bevacizumab in mCRC. Serum samples were analysed for 55 unique angiogenesis related proteins using a commercial proteome profiler array and a publicly available image analysis program for quantification. Samples were collected at baseline before induction treatment start, at start of maintenance treatment, and at end of treatment after tumour progression. MAIN RESULTS AND CONCLUSION:For eight proteins, the antibody array signals were below detection range in all patient samples. None of the proteins showed levels at baseline or at start of maintenance with strong evidence for correlation to time to progression (lowest nominal p-value 0.03). The dynamic ranges of protein levels measured during the induction treatment period and during the maintenance period were analysed separately for time trends. Evidence for changing trends (up/down) in the levels of MMP-8, TIMP-4 and EGF was observed both during response to induction treatment and at progressive disease, respectively. For three of the proteins (IL-8, Activin A and IGFBP-2), weak evidence for correlation between increasing protein levels during induction with chemotherapy and bevacizumab and time to progression was observed. In conclusion, semi-quantitative profiling of angiogenesis related proteins in patient serum may be a versatile tool to screen for protein patterns aiming at identifying resistance mechanisms of anti-angiogenic treatment in patients with mCRC.

Dataset Information

Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.

Publications

Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.

Similar Datasets

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