[HTML][HTML] VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2

NG Gavalas, M Tsiatas, O Tsitsilonis, E Politi… - British journal of …, 2012 - nature.com
NG Gavalas, M Tsiatas, O Tsitsilonis, E Politi, K Ioannou, AC Ziogas, A Rodolakis, G Vlahos…
British journal of cancer, 2012nature.com
Background: Vascular endothelial growth factor action in tumour angiogenesis is well
characterised; nevertheless, it functions as a key element in the promotion of the immune
system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on
T-cell activation and through which type of VEGF receptor it exerts this effect on cells
isolated from ovarian cancer patients' ascites. Methods: T cells isolated from the ascites of
ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 …
Abstract
Background:
Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system’s evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients’ ascites.
Methods:
T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed.
Results:
The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3+ T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells.
Conclusion:
Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.
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