ICAM-1 and VCAM are induced by ionizing radiation on lymphatic endothelium

Publication date: Available online 7 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): María E. Rodriguez-Ruiz, Saray Garasa, Inmaculada Rodriguez, Jose Luis Solorzano, Benigno Barbes, Alba Yanguas, Alvaro Teijeira, Iñaki Etxeberria, J. Javier Aristu, Cornelia Halin, Ignacio Melero, Ana Rouzaut
Radiotherapy exerts powerful biological effects on tumor tissue and the surrounding non-malignant microenvironment. Although radiation therapy has been conventionally used for its tumor cytocidal effect, its additional participation in the modulation of the immune properties of the tumor stroma is gaining momentum. Therefore, tumor vasculature is of key importance because reeducation of the immune tumor microenvironment including reshaping leukocyte migration across vascular barriers deserves attention if therapeutic efficacy is to be fully understood. For instance, radiotherapy has been reported to induce expression of the integrin ligands ICAM-1 and VCAM on the endothelium of blood vessels thereby guiding leukocyte trafficking. In this study, we have explored such effects on lymphatic endothelial cells. In culture, these cells experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors when subjected to irradiation. In freshly excised human carcinomas ICAM-1 and VCAM induction occurred on both blood and lymphatic vessels. In transplanted mouse tumors derived from B16-OVA and syngeneic MC38 cell lines, ICAM-1 and VCAM were also induced on lymphatic and blood vessels by a single radiotherapy fraction in a dose-dependent manner. In human cultured primary lymphatic endothelial cells, TGFβ appears to be involved in the integrin-ligand induction that mediates increased adhesion to CD8⁺ T lymphocytes. Moreover, irradiation of human tumor tissue leads to clustering of CD8⁺ tumor infiltrating lymphocytes with LVs. Overall, the pro-adhesive effects of ionizing radiation on lymphatic and blood vessels in tumors are likely to be important for modulating leukocyte trafficking in tumors.



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