Local low dose irradiation triggers tumor infiltration by adoptively transferred and host T lymphocytes and enhances immunotherapy in mice [Elektronische Ressource] / presented by Tobias Julian Seibel

DISSERTATION Submitted to the Combined Faculties of the Natural Sciences and Mathematics of the Ruperto-Carola-University of Heidelberg, Germany for the degree of Doctor of Natural Sciences Presented by: Diplom-Biologe Tobias Julian Seibel Born in Pirmasens, Germany thOral examination: October 19 , 2010 Local Low Dose Irradiation Triggers Tumor Infiltration by Adoptively Transferred and Host T Lymphocytes and Enhances Immunotherapy in Mice Referees: 1. Prof. Dr. Volker Schirrmacher 2. Prof. Dr. Michael Eisenhut Abstract The use of immunotherapeutic approaches for the treatment of cancer is limited be-cause of the intrinsic resistance of tumors to T cell infiltration and effector function. Enhanced infiltration of T cells can be achieved by inducing an activated tumor mi-croenvironment utilizing whole body irradiation in mice. However, radiotherapy of human cancer with high doses is not applicable in some patients due to complica-tions associated with organ damage. We hypothesized that locally applied low dose irradiation is sufficient to create a niche favoring immune effector cell entry to the tu-mor. The RIP1-Tag5 (RT5) transgenic mouse model expressing the simian virus 40 de-rived T antigen (Tag) as a model tumor antigen was employed for this study.