Vascular endothelial growth factor (VEGF) is an important regulator of physiological and pathological angiogenesis. Besides malignant and stromal cells, local immune cells shape VEGF signalling in the tumour microenvironment. Aminobisphosphonates such as zoledronic acid (Zol) are drugs known to inhibit osteoclast activity and bone resorption, but also have immunomodulatory and anti-tumour effects. These properties have been linked previously to the down-regulation of VEGF and interference with tumour neo-angiogenesis. It was therefore surprising to find that treatment with Zol in combination with low-dose interleukin (IL)-2 increased serum VEGF levels in cancer patients. In this study we aimed to characterize the effect of Zol and IL-2 on VEGF signalling of blood-derived immune cells in vitro. Upon stimulation with IL-2, T cells and natural killer (NK) cells increase production of VEGF consecutively to the release of proinflammatory interferon (IFN)-gamma, and Zol accelerates this response specifically in gamma delta T cells. VEGF can, in turn, be antagonized by soluble VEGF receptor (sVEGFR)-1, which is released depending on stimulatory conditions and the presence of monocytes. Additionally, malignant cells represented by leukaemia and lymphoma cell lines produce VEGF and some release sVEGFR-1 simultaneously. Our findings indicate a mechanism by which the VEGF and the sVEGFR-1 production by immune cells regulates local VEGF signalling. Therefore, immunotherapeutic interventions may enable both pro-as well as anti-tumour effects via immune cell-mediated alterations of VEGF homeostasis.
机构:Univ Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, England
Bingle, L
;
Brown, NJ
论文数: 0引用数: 0
h-index: 0
机构:Univ Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, England
Brown, NJ
;
Lewis, CE
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, EnglandUniv Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, England
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Edelbauer, Monika
;
Datta, Dipak
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Datta, Dipak
;
Vos, Ingrid H. C.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Vos, Ingrid H. C.
;
Basu, Aninda
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Basu, Aninda
;
Stack, Maria P.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Stack, Maria P.
;
Reinders, Marlies E. J.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Reinders, Marlies E. J.
;
Sho, Masayuki
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Sho, Masayuki
;
Calzadilla, Katiana
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Calzadilla, Katiana
;
Ganz, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA USA
Harvard Univ, Sch Med, Dept Med, Boston, MA USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Ganz, Peter
;
Briscoe, David M.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Eubank, TD
;
Roberts, R
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Roberts, R
;
Galloway, M
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Galloway, M
;
Wang, YJ
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Wang, YJ
;
Cohn, DE
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Cohn, DE
;
Marsh, CB
论文数: 0引用数: 0
h-index: 0
机构:
Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USAOhio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
机构:Univ Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, England
Bingle, L
;
Brown, NJ
论文数: 0引用数: 0
h-index: 0
机构:Univ Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, England
Brown, NJ
;
Lewis, CE
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, EnglandUniv Sheffield, Sch Med, Div Genom Med, Tumor Targeting Grp, Sheffield S10 2RX, S Yorkshire, England
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Edelbauer, Monika
;
Datta, Dipak
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Datta, Dipak
;
Vos, Ingrid H. C.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Vos, Ingrid H. C.
;
Basu, Aninda
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Basu, Aninda
;
Stack, Maria P.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Stack, Maria P.
;
Reinders, Marlies E. J.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Reinders, Marlies E. J.
;
Sho, Masayuki
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Sho, Masayuki
;
Calzadilla, Katiana
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Calzadilla, Katiana
;
Ganz, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA USA
Harvard Univ, Sch Med, Dept Med, Boston, MA USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Ganz, Peter
;
Briscoe, David M.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAChildrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Eubank, TD
;
Roberts, R
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Roberts, R
;
Galloway, M
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Galloway, M
;
Wang, YJ
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Wang, YJ
;
Cohn, DE
论文数: 0引用数: 0
h-index: 0
机构:Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
Cohn, DE
;
Marsh, CB
论文数: 0引用数: 0
h-index: 0
机构:
Ohio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USAOhio State Univ, Coll Med & Publ Hlth, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA