ESTRO 2023 - Abstract Book

S2019

Digital Posters

ESTRO 2023

extracted TIME. 3. Registration of reconstructed IHC images over µ CT scans : we obtained a 3D map of CD8+ TILs, which was subsequently readjusted to the anatomical volume obtained by µ CT. IHC images were superimposed over µ CT scans to correlate the spatial distribution of immune cells with µ CT textural parameters. Conclusion We generated a reproducible µ CT radiomic platform able to non-invasively decipher TIME features in murine models. Exploiting, in finely controlled laboratory settings, the potential of radiomics to timely assess distinct immune parameters and predict treatment outcome, may partly overcome the limitations observed in clinical practice and implement the personalization of therapeutic strategies. and correlated with distinct

PO-2244 The effect of hyperthermia and radiation therapy sequence on the immune phenotype of breast cancer

A. Sengedorj 1,3 , M. Hader 2 , B. Frey 2,4 , E.M. Scutigliani 5 , F. Cerna Lobo 6 , P.M. Krawczyk 5 , L. Heger 7 , D. Dudziak 7 , R. Fietkau 2 , O.J. Ott 2 , S. Scheidegger 8 , S.M. Barba 9 , U.S. Gaipl 2,3 , M. Rueckert 2,3 1 Universitätsklinikum Erlangen , Department of Radiation Oncology, Erlangen, Germany; 2 Universitätsklinikum Erlangen, Department of Radiation Oncology, Erlangen, Germany; 3 Universitätsklinikum Erlangen, Translational Radiobiology, Erlangen, Germany; 4 Universtitätsklinikum Erlangen, Translational Radiobiology, Erlangen, Germany; 5 Amsterdam University Medical Centers , Department of Medical Biology, Amsterdam , The Netherlands; 6 Amsterdam University Medical Centers , Department of Medical Biology, Amsterdam, The Netherlands; 7 Universitätsklinikum Erlangen, Department of Dermatology, Erlangen, Germany; 8 Zurich University of Applied Sciences , ZHAW School of Engineering , Winterthur, Switzerland; 9 University of Fribourg , Faculty of Medicine and Science , Fribourg, Switzerland Purpose or Objective Hyperthermia (HT) is a cancer treatment that increases the tumor temperature to 39-44°C, and it is a potent radiotherapy sensitizer (RT). HT has various effects on the innate and adaptive immune system and can potentially strengthen systemic antitumor immune responses. However, little is known about how different temperatures and, in particular, the sequence of HT and RT affect the immune phenotype in vitro and in vivo. And how the dendritic cells (DC) which is the main connector of the innate and adaptive immune system get affected by HT and RT needs investigation as well. Materials and Methods To this end, human MDA-MB-231 and MCF7 breast cancer cells were exposed to different temperatures of HT (39, 41, and 44 °C), alone or in combination with RT (2 x 5 Gy) in different sequences. Cell death and expression of immune checkpoint molecules (ICMs) were then analyzed by multicolor flow cytometry. Additionally, human monocyte-derived dendritic cells (hmDCs) were differentiated and co-cultured with the treated cancer cells, then the expression of DC activation markers was analyzed. Results Our results showed that, for both cell lines, RT was the main inducer of cell death with apoptosis being the most prominent form of cell death in MCF7 cells, and both apoptosis and necrosis for MDA-MB-231 cells. However, there was no significant difference between the treatment sequences, as determined by measuring cell death. The expression of immune- suppressive ICMs, including PD-L1, PD-L2, and HVEM significantly increased 120h after RT and HT treatment in MCF7 cells. In MDA-MB-231 cells, PD-L2 was upregulated after RT combined with HT (41 and 44°C). Likewise, generally high expression of ICMs is observed after combining RT and HT, however, this was not affected by the treatment sequence. Furthermore, the co-culture of hmDCs with treated cancer cells had no impact on the expression of DC activation markers. Conclusion In conclusion, the sequence of HT and RT doesn’t strongly affect the immune phenotype of breast cancer cells. Noteworthy, the combined treatments do result in upregulation of immune suppressive ICMs. This may suggest that, in multimodal treatment settings, immune checkpoint inhibitors could be beneficially combined with HT and RT. Also, as the treatments had no impact on the activation state of dendritic cells, we hypothe that RT and HT combination might affect the immune system in the effector phase rather than in the priming phase of the immune response, although this should be further analyzed in vivo. In our future experiments, we will investigate the DNA damages caused by RT and HT combination, and how it affects the immune response. The dynamic and different forms of DNA damage will be examined. Specifically, would HT and RT induce micronuclei, which is a result of unrepaired double-strand break, and whether this unresolved DNA damage burden further affects the anti-tumor immunity and the expression of ICMs will be investigated. P. Bergeron 1,2 , M. Dos Santos 3 , L. Sitterle 4 , W. Liu 4 , L. Meziani 4 , M. Benadjaoud 3 , J. Lavigne 3 , M. Gerbé de Thore 5 , C. Clémenson 5 , C. Schott 5,2 , E. Deutsch 5 , F. Milliat 3 , M. Mondini 5 1 Institut Gustave Roussy, Inserm U1030 , Molecular Radiotherapy and Therapeutic Innovation , Villejuif, France; 2 Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; 3 Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Radiobiology of Medical Exposure Laboratory (LRMed), Fontenay-aux-Roses, France; 4 Institut Gustave Roussy, Inserm U1030 , Molecular Radiotherapy and Therapeutic Innovation, Villejuif, France; 5 Institut Gustave Roussy, Inserm U1030, Molecular Radiotherapy and Therapeutic Innovation, Villejuif, France PO-2245 In situ abscopal effect: synergistic efficacy of immunotherapy and partial tumor irradiation

Purpose or Objective