Unit:
Τομέας ΚλινικοεργαστηριακόςLibrary of the School of Health Sciences
Dissertation committee:
Δημόπουλος Μελέτιος-Αθανάσιος Καθηγητής, Μπάμιας Αριστοτέλης Αναπλ. καθ., Ροδολάκης Αλέξανδρος Αναπλ. καθ.
Original Title:
Επίδραση του αυξητικού παράγοντα του αγγειακού ενδοθηλίου (VEGF) στους υποπληθυσμούς των λεμφοκυττάρων στον καρκίνο ωοθηκών
Translated title:
Effects of vascular endothelial growth factor on subpopulations of lymphocytes in ovarian cancer
Summary:
INTRODUCTION: Recent data suggest that VEGF contributes to tumor growth not
only by promoting angiogenesis but also by an indirect mechanism of regulation
of T cells involved in the immune response against the tumor.
AIM: The aim of the present thesis is to study the possible direct effect of
vascular endothelial growth factor (VEGF) on T cells subpopulations of ovarian
cancer patients.
MATERIALS AND METHODS: Ascitic fluids and peripheral blood samples were
collected from 15 patients and peripheral blood samples from 10 healthy
donors.. T cells were expanded in cultures, with or without VEGF. The
expression of VEGF receptors was assayed by flow cytometry, immunocytochemistry
and Western blotting. Cultured T cells were also tested for their cytotoxic
activity, and culture supernatants were measured by enzyme linked immunosorbent
assay for VEGF.
RESULTS-DISCUSSION: Τhe addition of VEGF in cultures significantly reduced the
number and proliferation rate of T cells. CD3+ T cells expressed VEGFR-2 and
secrete VEGF on their surface upon activation. We also showed that VEGF
suppresses T cell proliferation through VEGFR-2, as the addition of
anti-VEGFR-2 mAb fully restored the VEGF-induced suppression of T cell
proliferation. Furthermore, we showed that VEGF significantly reduced the
cytotoxic activity of T cells. to in their culture environment.
We have demonstrated for the first time that T lymphocytes secrete VEGF and
express VEGFR-2 on their surface in response to their activation. This in turn,
promotes the suppression of activated T cells by the VEGF produced by the
tumour, thus suggesting an immunosuppressive effect.
Keywords:
VEGF, VEGFR-2, Ovarian cancer, Immune suppression
Number of references:
156