ESTRO 2023 - Abstract Book

S137

Saturday 13 May

ESTRO 2023

The Netherlands

Abstract not available

SP-0185 What can brachytherapy achieve in dose escalation? A. Gomez Iturriaga Spain

Abstract not available

SP-0186 Where does SBRT stand in dose escalation? Is combination therapy with brachytherapy the optimal solution? A. Loblaw 1 1 Sunnybrook Health Sciences Centre, Radiation Oncology, Toronto, Canada Abstract Text External beam radiotherapy, brachytherapy boost and androgen deprivation therapy is the evidence-based standard of care for unfavourable (unfavourable intermediate and high) risk prostate cancer. The data supporting the use of elective whole pelvic radiotherapy is conflicting with the definitive study (NRG 0924) not expected to read out for another decade. There are good data to support the use of stereotactic body radiotherapy (SBRT) in intermediate risk patients but limited data for unfavourable risk patients. We will review the prospective studies that have been reported for these patients using SBRT as well as the studies that have been completed or are enrolling that will provide evidence for the use of SBRT (including the role of microboosting).

Symposium: Radiotherapy-immunotherapy combinations - How does the tumour microenvironment keep tumours cold?

SP-0187 Oncogene-mediated suppression of immune responses M. van Vugt 1 1 University Medical Center Groningen, Medical Oncology, Groningen, The Netherlands

Abstract Text Genomic instability and inflammation are intricately connected hallmark features of cancer. DNA damage in tumor cells can occur due to cancer-associated DNA repair defects, oncogene-induced replication stress or genotoxic cancer treatments. Unresolved DNA lesions can instigate signaling through the cGAS/STING pathway. The subsequent inflammatory signaling provides both tumor-suppressive as well as tumor-promoting traits. To prevent clearance by the immune system, cancer cells need to adapt to escape immune surveillance. Currently, it is unclear how genomically unstable cancers, including triple-negative breast cancer (TNBCs), are rewired to escape immune clearance. I will discuss our studies on the mechanisms by which genomic instability triggers inflammatory signaling and describe adaptive mechanisms by which cancer cells can 'fly under the radar' of the immune system, and the therapeutic consequences thereof. Specifically, I will discuss the strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of TNBC proficient or deficient of breast cancer type 1 susceptibility gene (BRCA1), MYC overexpression dramatically decreased lymphocyte infiltration in tumors, along with immune signature remodeling. MYC-mediated suppression of inflammatory signaling induced by BRCA1/2 inactivation was confirmed in human TNBC cell lines. Moreover, MYC overexpression prevented the recruitment and activation of lymphocytes in both human and mouse TNBC co-culture models. Chromatin-immunoprecipitation-sequencing revealed that MYC, together with its co-repressor MIZ1, directly binds promoters of multiple interferon-signaling genes, resulting in their downregulation. Together, our data revealed that MYC suppresses innate immunity and facilitates tumor immune escape, explaining the poor immunogenicity of MYC- overexpressing TNBCs. SP-0188 Mechanisms underlying immune suppression by hypoxia in cervix cancer patients during clinical radiotherapy H. Lyng 1 1 Oslo University Hospital, Department of Radiation Biology, Oslo, Norway Abstract Text The tumor microenvironment contains immune cells, like T-cells and macrophages, and stroma that can promote or hinder cancer progression. This immune response differs among tumors, and has been associated with radiotherapy outcome. The radiation treatment itself can induce an immune response towards cancer cells, and the potential of combining radiotherapy with immunotherapy is an attractive strategy. In preclinical studies, hypoxia has been associated with suppression of the anti-tumor immune response, but little attention has been paid to hypoxia in radiation-immune based combination strategies in the clinic. In this talk, I will present the prognostic value of combining pretherapy hypoxia and immune information in outcome prediction of 290 cervical cancer patients. Further, to better understand the relationship between immune responses, hypoxia and radiotherapy outcome, we have analysed tumor samples collected before and during treatment (after 10 Gy) of 100 cervical cancer patients, using RNA-sequencing and digital histopathology. Results from these studies will be discussed. SP-0189 Immune escape in solid tumours: How radiation-induced immune checkpoints change the playing field E. Wennerberg 1 1 Institute of Cancer Research, Radiotherapy and Imaging, London, United Kingdom Abstract Text As solid tumours evolve under immunological pressure, cancer cells are selected for their ability to evade immune attack, either by hiding from or by directly counteracting the immune attack. By subverting mechanisms of immune homeostasis,