Radiation therapy (RT) induces nucleic acid sensing followed by cancer cell-intrinsic interferon (IFN-I) responses in various cancers. However, combining RT with immunotherapy in glioblastoma has failed to improve patient survival, suggesting robust immunosuppression. Our previous findings showed that RT induces a metabolic shift towards fatty acid synthase (FASN)-mediated lipid synthesis, supporting glioblastoma survival (De Martino, et al. Cancer Lett. 2023). Since fatty acid metabolism hampers IFN-I responses in viral immunity, we hypothesized that FASN might similarly inhibit IFN-I in irradiated glioblastoma, acting as an immune evasion mechanism.

Mara De Martino¹, Camille Daviaud¹, María Cecilia Lira¹, Matthew H. Ingalls², Fabian Schneider³, Regan Baird³, James Mansfield³, J. Spencer Schwarz², Oliver Braubach² and Claire Vanpouille-Box^1,4

1. Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA
2. Bruker Spatial Biology, Saint Louis, MO, USA
3. Visiopharm A/S, Horsholm, Denmark
4. Sandra and Edward Meyer Cancer Center, New York, NY, USA