ESTRO 2020 Abstract book

S1067 ESTRO 2020

(BED) of photon, proton and carbon irradiation, as defined by clonogenic survival, revealed similar effects on leukocyte migration. Carbon ion and photon radiation- induced SASP induced CD4 T cell recruitment towards pancreatic cancer cells and abrogated monocyte recruitment towards melanoma cells. Conclusion Our findings may help to better understand the effects of photon and particle radiation on bystander immune cells, with possible implication for combined immunotherapy applications. PO‐1820 Repolarized macrophages, induced by SRS and anti‐PD1, mediate long‐term survival in murine glioma A. Stessin 1 , M. Clausi 1 , S. Ryu 1 1 Stony Brook University Hospital, Radiation Oncology, Stony Brook- NY, USA Purpose or Objective Glioblastoma multiforme (GBM) is a deadly brain tumor with a short expected median survival, despite current standard-of-care treatment. We explore the combination of high single dose radiation therapy and immune checkpoint inhibitor therapy as a novel treatment strategy for GBM. Material and Methods Mice bearing GL261 intracranial glioma implants were treated with anti-PD1, stereotactic dose RT, or combination thereof, in the presence or absence of T-cell, macrophages, and microglia suppression. MRI was used to monitor tumor growth. Gene expression arrays, immunohistochemistry, and flow cytometry were used to analyze immune cell population dyniamics under conditions of interest. Results We show combined treatment SRS and antiPD1 treatment to be highly effective with a 75% complete pathologic response and dramatically improved survival outcomes in glioma xenograft-bearing mice. We also investigate the roles of different immune cell types. We find both CD8+ T- cells and macrophages to be necessary for the full effect of combined therapy, with T lymphocytes appearing to play a role early on and macrophages mediating a later phase of the combined treatment effect. The combined treatment appears to trigger macrophage repolarization, increasing M1/M2 ratio. Conclusion These findings point to a novel immunologic mechanism underlying the interaction between radiotherapy and immunotherapy. They also provide the basis for clinical investigation of immunogenic dose radiation in combination with immune checkpoint blockade as a potential treatment approach for newly diagnosed high grade gliomas. PO‐1821 Investigating immune microenvironment effects of radiotherapy in pre‐clinical prostate cancer models Y. Philippou 1 , H. Sjoberg 2 , E.A. Murphy 2 , K. Jones 1 , A. Gordon-Weeks 1 , G. McKenna 1 , G. Uzi 3 , V. Cerundolo 3 , I.G. Mills 2 , F.C. Hamdy 2 , R.J. Muschel 1 , R.J. Bryant 1 1 University of Oxford, Oxford Institute for Radiation Oncology, Oxford, United Kingdom ; 2 University of Oxford, Nuffield Department of Surgical Sciences, Oxford, United Kingdom ; 3 University of Oxford, MRC Human Immunology Unit - Weatherall Institute of Molecular Medicine, Oxford, United Kingdom Purpose or Objective Hypo-fractionated radiotherapy (HF-RT) can enhance anti- tumour immunity, but it is unclear whether this effect can be induced, or harnessed in a multi-modality therapy approach, in the treatment of high-risk locally advanced prostate cancer (PCa). We investigated the temporal

level on CD4 + Foxp3 + cells increased after implantation then it showed a decreasing tendency. The fraction of MDSCs showed a significant decrease at all time points up to 24 months. The level of NK cells increased significantly and remained elevated even 36 months after therapy completion. Subpopulations of dendritic cells (DCs, CD123 + , CD11c + ) were elevated before RT, remained elevated up to 6 months after seed implantation and started to decrease to control levels thereafter. HDR RT patients experienced the less urinary inconveniences, IPSS and QoL was the worst directly after teletherapy (16.8 ± 1.4 and 3.0 ± 1.3 in average, respectively). ≥ G2 acute GU side effects (69.9%)and ≥ G2 late GU toxicity (50.0%) were the most frequent after seed therapy. Conclusion These data indicate a radiation effect on the homeostasis of CD4 + cells, persistently elevated Treg levels as a result of seed brachytherapy, temporarily increased fraction of CTLA4 + CD4 + cells with inhibitory phenotype, a persistent effect of radiation on MDSCs, long-lasting increase in the fraction of NK cells even after the end of RT, a direct effect of therapeutic dose accumulation in the normalisation of DC levels. HDR RT caused the less ≥G2 GU and GI acute and late side effects. These values changed in parallel with cytogenetic parameters, suggesting their use as predictive indicator of toxicity. The follow-up period is 5 years, data processing regarding immunological values in the other arms is still in progress. PO‐1819 Leukocyte migration towards particle radiation‐induced senescence‐associated secretory phenotypes T. Walle 1 , T. Beikert 2 , J. Kraske 2 , T. Trinh 2 , A. Tietz 2 , J. Debus 3 , P. Huber 2 1 dkfz/University Hospital/NCT, Oncology/Molecular and Radiation Oncology, Heidelberg, Germany ; 2 dkfz/University Hospital, Molecular and Radiation Oncology, Heidelberg, Germany ; 3 dkfz/University Hospital/HIT, Radiation Oncology, Heidelberg, Germany Purpose or Objective Cytotoxic therapies, such as radiation therapy (RT), induce cellular senescence and subsequent secretion of soluble mediators from tumor cells, which are collectively called the senescence-associated secretory phenotype (SASP). SASP can affect both tumor cells and bystander cells, such as leukocytes and affect their migratory behavior. Here, we comprehensively assessed the effects of photon and particle radiation induced SASP on leukocyte migration. Material and Methods Human tumor cell lines of different tumor type were irradiated using an X-ray machine (Faxitron, Multirad) or with protons or carbon ions using a cyclotron (Heidelberg Ion Therapy Center). Biologically effective doses were determined by clonogenic assays for photon, proton and carbon ion radiation. Cellular senescence was determined by β-galactosidase staining and automated quantification of microscopy images. Tumor cell apoptosis was assessed by Annexin V and 7AAD flow cytometric staining. Chemokine release was analyzed by flow-cytometry based multiplex bead arrays and subsequent leukocyte migration was determined by modified Boyden chamber assays. Results High single-dose photon irradiation induced cellular senescence and SASP with release of different chemokines and growth factors in solid tumor cell lines of different tumor type. SASP limited proliferation and reinforced radiation-induced apoptosis of tumor cells. We observed general and cell line specific effects of SASP on leukocyte migration: SASP triggered migration of NK cells and abrogated migration of monocytes towards different solid tumor cell lines. Higher migration of CD4+ T cells was observed towards pancreatic cancer cells. Comparison of SASPs induced by physical and biological equivalent doses