ESTRO 2024 - Abstract Book

S5176

Radiobiology - Immuno-radiobiology

ESTRO 2024

Conclusion:

Incorporating immunotherapy into induction chemoradiotherapy in patients with T3-4N0-1 NSCLC augments type-1 cell-mediated immunity, accompanied by elevated levels of proliferating cytotoxic CD8 and regulatory T cells within TDLN. Notably, higher radiation doses correlated with increased activation of CD8 T cells and regulatory T cells in the cohort receiving immunotherapy. Spatial genomics analyses revealed a robust type-1 cell mediated immune response in the INCREASE group, coupled with heightened expression of collagen and histone in high-dose TDLN, consistent with elevated fibrosis and tissue repair following intensified radiation. However, further validation of these findings using quantitative pathology imaging is imperative.

Keywords: TDLN, spatial transcriptomics, NSCLC

References:

Dickhoff C, et al. Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable T3-4N0-1 non-small cell lung cancer: the INCREASE trial. BMC Cancer. 2020 Aug 14;20(1):764.

1483

Digital Poster

Disruption of redox homeostasis triggers inflammatory signaling through the release of cytosolic DNA

Lucie Malbeteau 1 , Emily Poulton 1,2 , Vishal Pandya 1,3 , Alina Jaglanian 1 , Marianne Koritzinsky 1,4,3

1 University Health Network, Princess Margaret Cancer Centre, Toronto, Canada. 2 University of Toronto, Medical Biophysics, Toronto, Canada. 3 University of Toronto, Institute of Medical Science, Toronto, Canada. 4 University of Toronto, Radiation Oncology, Toronto, Canada

Purpose/Objective:

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease associated with poor clinical prognosis and limited response to treatments. This treatment resistance is mostly driven by the presence of multiple suppressive immune populations in a physically dense fibrotic tumour microenvironment (TME) that shield PDAC from conventional antitumor therapies. Interestingly however, PDAC cells are surrounded by a stroma already infiltrated with cytotoxic T-cells, only requiring activation. Our current work aims to reactivate tumor-infiltrating effector T cells to sensitize PDAC to radiation and immune therapy. The high metabolic activity of fast-growing pancreatic cancer cells leads to high production of reactive oxygen species (ROS). Tumor cells have evolved mechanisms of ROS detoxification to maintain redox balance and avoid cell death. As such, disrupting redox homeostasis by targeting those systems represents a vulnerability for cancer cells that may be exploited. We identified the antioxidant peroxiredoxin 4 (PRDX4) as a promising target in PDAC. PRDX4 loss causes high levels of ROS and DNA damage leading to cell death in vitro and increased survival of mice bearing PRDX4-depleted tumors. Moreover, targeting PRDX4 significantly sensitizes PDAC cells and tumors to ionizing radiation [1].