ESTRO 2024 - Abstract Book

S5365

Radiobiology - Tumour biology

ESTRO 2024

investigate alterations in gut microbiota and metabolites. Flow cytometry and immunofluorescence were performed to assess tumor immune microenvironment.

Results:

HFD reduced RT efficacy with increased tumor volume, pathological score and cellular proliferation in orthotopic rectal cancer model compared with control diet. Antibiotics treatment attenuated tumor growth in HFD-fed mice receiving RT. Gut microbial dysbiosis was observed in HFD-fed mice with significant differential abundance of bacterial species, including the enrichment of Fusobacterium ulcerans and Fusobacterium gastrosuis, and depletion of Bifidobacterium animals. Furthermore, antibiotics-induced gut microbiome-depleted mice gavaged with fecal samples of HFD-fed mice exhibited radiation resistance with increased tumor volume following RT, indicating gut microbiota contributes to HFD-induced radiation resistance in rectal cancer. Moreover, metabolomic analysis revealed that bile acids biosynthesis was significantly upregulated in HFD-fed mice with increased taurochenodeoxycholic acid (TCDCA) levels, which was confirmed to promote colony formation and inhibit apoptosis in CRC cell lines receiving RT. Meanwhile, decreased levels of hydantoin-5-propionic acid and indole-2-carboxylic acid (I2CA) were also observed in HFD-fed mice receiving RT. Moreover, HFD increased regulatory T cells and PD-1+CD8+ T cells infiltration and decreased interferon-γ expression in CD8+ T cells in tumor tissues compared with control diet.

Conclusion:

HFD promotes radiation resistance in rectal cancer through inducing gut microbial dysbiosis, metabolomic dysregulation with elevated TCDCA, and regulatory T cells and PD-1+CD8+ T cells infiltration in mice.

Keywords: High fat diet, gut microbiota, radiotherapy

1062

Digital Poster

Micro-dissected tumour tissues-on-chip; a tool for translational radiation oncology

Maryam Ziaee 1,2 , Gabriel Pagé 1 , Julie Lafontaine 1 , Francis Rodier 1,3 , Thomas Gervais 4,1 , Philip Wong 5,1

1 Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Institute Cancer De Montréal, Montreal, Canada. 2 École polytechnique de Montreal, Biomedical Engineering, Montreal, Canada. 3 Université de Montréal, Département de radiologie, radio-oncologie et médecine nucléaire, Montreal, Canada. 4 École polytechnique de Montreal, Engineering Physics, Montreal, Canada. 5 Princess Margaret Cancer Centre, Radiation Oncology, Toronto, Canada

Purpose/Objective: