Description
Glioblastoma multiforme (GBM) is one of the most
aggressive and treatment-resistant brain tumors,
characterized by rapid proliferation, diffuse infiltration, and poor
prognosis. Despite current standards of care—surgical resection
followed by radiotherapy or chemotherapy. A major obstacle to
treatment success is the presence of hypoxic tumor niches that
harbor cells with metastatic phenotypes and intrinsic resistance to
conventional radiation. These regions are poorly oxygenated,
genetically unstable, and less responsive to
therapies, highlighting the urgent need for new strategies that
overcome radio resistance and engage anti-tumor immunity.
In this project, we investigated proton therapy as a precision
modality capable of delivering high linear energy transfer (LET)
radiation with minimal damage to surrounding healthy tissue.
Unlike conventional X-rays, proton beams deposit most of their
energy at the Bragg peak, enabling spatially localized dose
delivery. Beyond this physical advantage, we hypothesized that
proton therapy could stimulate immune responses through
activation of the cGAS–STING pathway, which detects cytosolic
double-stranded DNA and initiates the production of interferon-
beta (IFNβ), a key cytokine in anti-tumor immunity.
Using dose–response data from the U251 GBM cell line, we
incorporated IFN-β dose response into the FLUKA Monte Carlo
simulation framework. Simulations showed that a dose of
approximately 17 Gy optimized IFN-β induction without
triggering TREX1, a DNA exonuclease known to suppress immune
signaling at higher doses. The biological dose was modulated to
selectively cover a virtual subregion within the GTV, suggesting
the potential to stimulate localized immune responses in
treatment-resistant tumor microenvironment. These findings
support the dual role of proton therapy in delivering precise
radiation while also enhancing immunogenicity, offering a
promising foundation for future biologically guided radiotherapy
strategies in GBM. Further validation through in vitro
experiments and integration with immunotherapy could help
translate this approach into clinical protocols and expand its
relevance beyond GBM to other poorly immunogenic tumors
| Technical Track | Nuclear Applications and Radiation Processing |
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