ESTRO 36 Abstract Book

S548 ESTRO 36 _______________________________________________________________________________________________

combined with EBRT on lung metastasis from esophageal cancer. The representative optical images show lung metastatic burden detected by D-luciferin assay.

7 by adding tumor necrosis factor alpha (TNFα) to the culture medium. Differentiation and maturation of DCs was assessed on day 2, 9 and 12 by staining of the cell surface molecules CD14, CD83, CD80, CD86 and HLA-DR via flow cytometry. Functional analysis of irradiated DCs was performed through FITC-labelled phagocytosis assay. Results No major significant changes in the immune profile during differentiation of monocytes (CD14 high , CD83 low , CD86 low , CD80l ow , HLA-DR high ) into iDCs (CD83 low , CD86 low , CD80 medium , HLA-DR medium ) and mDCs (CD83 high , CD86 high , CD80 high , HLA-DR high ) were seen after treatment with different radiation doses (1x15 Gy, 5x2 Gy, 1x0.5 Gy) compared to the untreated control group. Functional analysis showed no difference in the phagocytotic capacity of irradiated iDCs and macs compared to the control group. Conclusion Our experiments reveal that after irradiation with different fractionations and doses maturation of DCs was unchanged compared to the control group. The capability for phagocytosis was unaffected after irradiation of DCs, indicating persistent functionality of the immune system. Additional RT-induced effects on the immunogenic potential of DCs will be investigated by using further functional assays (migration assay, mixed lymphocyte reaction assay). To investigate the effect of particle therapy, DCs will be irradiated with protons and carbon ions (C12) in future experiments. PO-0994 Integrin antagonistic drugs reveal different effectiveness in 2D monolayer vs. 3D spheroid culture V. Kopatz 1,2 , E. Selzer 1 , W. Dörr 1,2 1 Medical University of Vienna, Department for Radiation Oncology, Vienna, Austria 2 Medical University of Vienna, Christian Doppler Lab for Medical Radiation Research for Radiooncology, Vienna, Austria Purpose or Objective Preclinical evaluation of novel therapeutic substances, as well as the assessment of radiation effects, is frequently performed under standard 2D cell culture conditions. However, such monolayer cultures may fail with regard to representation of morphological in vivo conditions and their (radio)biological consequences. An alternative, in the latter aspect is the use of 3D in vitro models - like tumor spheroid culture - which are of intermediate complexity between standard in vitro monolayer cultures and in vivo tumor models. In spheroid culture, tumor cells grow in 3D aggregates that display greater similarity to in vivo tumor architecture and growth conditions, such as the presence of oxygen and nutrient gradients as well as more complex cellular interactions or 'in vivo-like” gene expression profiles. Depending on their size, multicellular spheroids may also display central hypoxic and/or necrotic areas and show quiescent and proliferating compartments. Thus spheroids often depict different behavior and sensitivity towards certain drugs or radiotherapeutic treatment as cells cultured as 2D monolayers. Especially for the study of surface receptors like integrins the 3D structure and environment is a critical aspect as these receptors transduce signals from the extracellular space to the inside, thus influencing different cell signaling pathways like cell survival, proliferation and invasion. Material and Methods Therefore in addition two standard 2D cell culture, 3D spheroid models were established with 518A2 and other melanoma cell lines for evaluation of their response to two different integrin antagonists, cilengitide and a novel integrin antagonist (NIA), as well as for the characterization of the effects of radiation treatment alone or in combination with the drugs.

Figure 2. The therapeutic efficacy of 188 Re-liposome combined with EBRT on lung metastasis from esophageal cancer. Low-dose whole lung EBRT with 3 consecutive daily fractions of 1 Gy was delivered followed by intravenous 188 Re-liposome (250 µCi) administration in combination group. N=3 for each group. Conclusion The combination of low-dose whole lung EBRT with systemic 188 Re-liposome administration might be a potential treatment modality for lung metastasis from esophageal cancer. Modulation of tumor microenvironment by the combination treatment is warranted in translational research. This proof-of-concept study needs to be validated by clinical investigation. PO-0993 Influence of radiotherapy on differentiation, maturation and functionality of dendritic cells L. König 1 , A. Gardyan 2 , J. Hörner-Rieber 1 , P. Huber 2 , K. Herfarth 1 , S. Rieken 1 Purpose or Objective Primary purpose of radiotherapy (RT) is elimination of cancer cells by inducing DNA-damage that either causes induction of tumor cell death or inhibition of the proliferating capacity of these cells. In addition, considerable evidence emerges that antineoplastic effects extend beyond these mechanisms. These secondary effects can contribute to anti-tumor responses in a local but also systemic manner via activation of the immune system: The role of dendritic cells (DCs) is well described to be essential for priming effective radiation-induced adaptive immunity. Through increased release of tumor- associated antigens (TAA) after RT, DCs are recruited and cross-presentation of TAA leads to activation of B- and T- lymphocytes, therefore playing a pivotal role in adaptive immune response and immunogenic cell death. However, there are still many hypotheses regarding the influence of RT on activation of the immune system. The aim of our experiments is to further characterize the impact of different radiation types and dosages on differentiation and functionality of DCs. Material and Methods Human CD14-positive monocytes were isolated from peripheral blood mononuclear cell samples of six individuals. In the presence of appropriate cytokine stimulation with Interleukin-4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF) monocytes were induced into immature DCs (iDCs) and later mature DCs (mDCs). Monocytes were irradiated with different photon radiation doses (1x15Gy, 5x2Gy, 1x0.5Gy) on day 0. Maturation to mDCs was induced on day 1 University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg, Germany 2 German Cancer Research Center- Heidelberg, Clinical Cooperation Unit Molecular Radiooncology-, Heidelberg, Germany