ESTRO 38 Abstract book

S60 ESTRO 38

infected stressed or dying cells. Over the last two decades, it has been widely recognized that in some contexts, sterile dying cells can trigger a potent innate immune response by exposing specific endogenous molecules, analogous to PAMPs, termed damage- associated molecular patterns (DAMPs). This concept has been successfully applied to cancer cells wherein specific therapeutic stimuli have been found to induce immunogenic cell death owing to spatio-temporally defined exodus of immunogenic DAMPs. In some contexts, this immunogenic cancer cell death has been found to have potent anticancer vaccination effect - a feature that has driven its translational popularity. However, there are still a number of basic questions regarding this concept that remain unaddressed. For instance, the PAMPs::DAMPs analogy has frequently raised a challenging question that remains unanswered i.e. can sterile dying cancer cells stimulate innate immunity by moderately mimicking pathogen defense response-like signaling? We have found that sterile immunogenic dying cancer cells indeed trigger (a cell-autonomous) pathogen response-like chemokine (PARC)-signature, which is quite reminiscent of chemokine patterns orchestrated by mammalian cells infected with bacteria or viruses. In fact this PARC signature was specific to immunogenic apoptosis but not to accidental necrosis or non-immunogenic apoptosis. This PARC-signature was found to pave way for neutrophils based phagocytic- targeting of dead/dying cancer cells and subsequent cytotoxic-targeting of residual (live) cancer cells. These observations shed light on the possible evolutionary basis for sterile immunogenic signaling during cancer cell death that needs further systematic investigation in near future. SP-0115 Immunogenic tumor cell death induced by chemoradiotherapy: a clinical point of view K. Mimura 1 , K. Kono 2 1 Fukushima Medical University, Department Of Gastrointestinal Tract Surgery- Department Of Blood Transfusion and Transplantation Immunology- Department of Advanced Cancer Immunotherapy- Department of Progressive Dohad Research, Fukushima, Japan; 2 Fukushima Medical University, Department of Gastrointestinal Tract Surgery, Fukushima, Japan Abstract text Chemoradiotherapy is generally thought to be immunosuppressive, either by depleting T- and NK-cells or by rendering them functionally inactive, leading to infectious complications and growth of residual tumors. However, radiation oncologists realized a rare phenomenon called the ‘abscopal effect’ where local irradiation on the tumor causes regression of metastases at sites distant from the irradiated area, although the underlying mechanisms of this effect have not been completely elucidated. In immunogenic tumor cell death (ICD), dendritic cells (DC) were activated by danger signals such as high mobility group box 1 (HMGB1) and calreticulin released by dying cells. The activated DC could then efficiently phagocytize and present cancer antigens, resulting in the induction of tumor specific cytotoxic T lymphocytes. There is a possibility that the abscopal effect is induced by the ICD process. Although we reported that chemoradiotherapy can induce ICD, there was limited information to translate this theory directly in a clinical setting. However, it was recently reported cases of abscopal effect in melanoma patients treated with radiotherapy and immune checkpoint inhibitors (ICI). Further, many clinical trials with this combination approach (radiotherapy and ICI) are ongoing in several types of tumor including melanoma, NSCLC, RCC, Glioblastoma, and HNSCC etc. In this session, I present cellular mechanisms underlying ICD induced by chemoradiotherapy from a clinical point of view.

as well as that the obtained object positions within the artifacts correspond to the simulated object positions. The mean deviations of the object positions (from average) were 0.2-0.3mm, proving that all sequences were suitable for localization of the objects.

Conclusion This study demonstrated that the MR artifact induced by an HDR source or a titanium needle could be simulated for the 4 investigated types of MR sequences (spoiled gradient echo, spin echo, bSSFP and bSSFP-SPAIR), valuable for object localization in clinical practice. This could be applied for fast 2D acquisitions as well as for volumes acquired using the MR sequences currently provided in the clinical scan protocol, leading to flexibility in the choice of MR sequences for guidance of HDR brachytherapy. 1.Beld E et al 2018 PMB 63 085002

Symposium: How to exploit Immunogenic cell death Mechanism in Radiotherapy

SP-0114 Immunogenic versus Non-Immunogenic Cell Death in Cancer A. Garg 1 , L. Vandenberk 2 , S. Fang 3 , P. De Witte 4 , P. Salven 3 , P. Agostinis 1 1 Ku Leuven, Cell Death Research and Therapy Cdrt Unit- Department Of Cellular And Molecular Medicine, Leuven, Belgium ; 2 ku Leuven, Department Of Microbiology And Immunology, Leuven, Belgium; 3 University Of Helsinki, Department Of Pathology, Helsinki, Finland ; 4 Ku Leuven, Department Of Pharmaceutical Sciences, Leuven, Belgium Abstract text Innate immune detection of cells damaged lethally by sterile or pathogenic stimuli is orchestrated through several different immune-modulatory, inflammatory and/or danger signals. In pathogenic contexts, inflammatory chemokines guided (rapid) recruitment of specific innate immune cells from circulation, and their pathogen-associated molecular patterns (PAMPs)- triggered activation is a distinct feature of pathogen-