Abstract 4015: Exposure of lymphatic endothelial cells to ionizing radiation increases the surface expression levels of integrin ligands

Abstract

Abstract Radiotherapy has been proven an efficacious tool to combat cancer by directly destroying tumor cells. However, effects of radiotherapy have been also described that occur through the re-education of the immune tumor microenvironment, being leukocyte traffic regulation across the tumor vasculature of key importance. Here, we address the effects that radiotherapy may be causing on the adhesive properties of the tumor lymphatic vasculature. To study this, we irradiated primary and immortalized human and murine lymphatic endothelial cells grown in vitro, and fresh tumor explants obtained from colon cancer patients. As a result, we observed dose- and time- dependent increases in the expression of the integrin counter-receptors ICAM-1 and VCAM on the surface of the tumor lymphatic endothelial cells. These effects are also observed in vivo on colon (MC38) and melanoma (B16) tumors transplanted into syngeneic mice and irradiated with a single dose of 20 Gy. These findings are consistent with increased ICAM-1 and VCAM expression levels on Lymphatic endothelial cells in tumor biopsies from cancer patients which were taken before and four weeks after fractionated radiotherapy, including head and neck, colon and oropharyngeal human carcinomas. While the TGFβ pathway was found to be involved in these effects, NF-κB inhibitors did not hamper ICAM-1 or VCAM induction. In summary, these results show ICAM-1 and VCAM surface expression was enhanced on lymphatic vessels after radiotherapy and may explain differential leukocyte traffic following irradiation. Citation Format: Maria E. Rodriguez-Ruiz, Saray Garasa, Inmaculada Rodriguez, Alba Yanguas, Álvaro Teijeira, Ignacio Melero, Ana Rouzaut. Exposure of lymphatic endothelial cells to ionizing radiation increases the surface expression levels of integrin ligands. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4015.