VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 SIGNALING AS A NOVEL MECHANISM OF T CELL SUPPRESSION IN TUMOR NEOANGIOGENESIS
https://doi.org/10.15789/1563-0625-2019-4-653-660
Abstract
The immunomodulatory activity of vascular endothelial growth factors (VEGFs) reveals a new role of neoangiogenesis in tumor development. Most of VEGF effects on T cells are mediated through the VEGF-R2 receptors. Placental growth factor (PlGF) belongs to the VEGFs family and is a selective ligand for VEGF-R1. In order to study the role of VEGF-R1-signaling in the regulation of T-cell functions, the effect of PlGF on the proliferation of donor T cell has been investigated. PlGF has been shown to inhibit the proliferation of T-lymphocytes in cultures of anti-CD3-stimulated mononuclear cells in a wide dose range, suppressing the proliferative response of both CD4 + and CD8 + T cells. The suppressive effect of PlGF was mediated through the direct interaction with VEGFR-1 on T-cells that was evidenced by the expression of VEGFR-1 by T-lymphocytes (especially after their activation) and by blocking the suppressive effect of PlGF with neutralizing anti-VEGFR-1 antibodies. Given the increased levels of PlGF in many tumors, this factor may play an important role in immunomodulation during tumor growth, mediating its effect through the VEGFR-1 signaling pathway.
Supporting agencies: Grant RFBR 18-44-540005
About the Authors
E. R. Chernykh
Research Institute of Fundamental and Clinical Immunology
Russian Federation
Russian Federation
PhD, MD, Professor (Medicine), Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy
630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., 14
Phone: 7 (383) 236-03-29
Fax: 7 (383) 222-70-28
O. Yu. Leplina
Research Institute of Fundamental and Clinical Immunology
PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy
630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., 14
M. A. Tikhonova
Research Institute of Fundamental and Clinical Immunology
PhD (Biology), Senior Research Associate, Laboratory of Cellular Immunotherapy
630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., 14
E. V. Batorov
Research Institute of Fundamental and Clinical Immunology
PhD (Medicine), Research Associate, Laboratory of Cellular Immunotherapy
630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., 14
A. A. Ostanin
Research Institute of Fundamental and Clinical Immunology
PhD, MD, Professor (Medicine), Main Research Associate, Laboratory of Cellular Immunotherapy
630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., 14
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51. Yang J., Yan J., Liu B. Targeting VEGF/VEGFR to modulate antitumor immunity. Front. Immunol., 2018, Vol. 9, p. 978.
52. Tchaikovski V., Fellbrich G., Waltenberger J. The molecular basis of VEGFR-1 signal transduction pathways in primary human monocytes. Arterioscler. Thromb. Vasc. Biol., 2008, Vol. 28, no. 2, pp. 322-328.
53. Ziogas A.C., Gavalas N.G., Tsiatas M., Tsitsilonis O., Politi E., Terpos E., Rodolakis A., Vlahos G., Thomakos N., Haidopoulos D., Antsaklis A., Dimopoulos M.A., Bamias A. VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2. Int. J. Cancer., 2012, Vol. 130, no. 4, pp. 857-864.
54. Voron T., Marcheteau E., Pernot S., Colussi O., Tartour E., Taieb J., Terme M. Control of the immune response by pro-angiogenic factors. Front Oncol., 2014, Vol. 4, p. 70.
55. Voron T., Colussi O., Marcheteau E., Pernot S., Nizard M., Pointet A.L., Latreche S., Bergaya S., Benhamouda N., Tanchot C., Stockmann C., Combe P., Berger A., Zinzindohoue F., Yagita H., Tartour E., Taieb J., Terme M. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med., 2015, Vol. 212, no. 2, pp. 139-148.
56. Yang J., Yan J., Liu B. Targeting VEGF/VEGFR to modulate antitumor immunity. Front. Immunol., 2018, Vol. 9, p. 978.
57. Ziogas A.C., Gavalas N.G., Tsiatas M., Tsitsilonis O., Politi E., Terpos E., Rodolakis A., Vlahos G., Thomakos N., Haidopoulos D., Antsaklis A., Dimopoulos M.A., Bamias A. VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2. Int. J. Cancer., 2012, Vol. 130, no. 4, pp. 857-864.
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Chernykh E.R., Leplina O.Yu., Tikhonova M.A., Batorov E.V., Ostanin A.A. VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 SIGNALING AS A NOVEL MECHANISM OF T CELL SUPPRESSION IN TUMOR NEOANGIOGENESIS. Medical Immunology (Russia). 2019;21(4):653-660. (In Russ.) https://doi.org/10.15789/1563-0625-2019-4-653-660
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