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2016 ; 7
(10
): 11137-50
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Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+
cells and IL-10 in metastatic breast cancer patients
#MMPMID26840567
Cattin S
; Fellay B
; Pradervand S
; Trojan A
; Ruhstaller T
; Rüegg C
; Fürstenberger G
Oncotarget
2016[Mar]; 7
(10
): 11137-50
PMID26840567
show ga
BACKGROUND: 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. METHODS:
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). RESULTS: 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. CONCLUSIONS: 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.