Eliminating Radioresistance With a Magnetic Ion-Generator by Simultaneously Augmenting DNA Damage and Diminishing...

Area of Science:

• Oncology
• Immunology
• Materials Science

Background:

• Radiotherapy (RT) efficacy relies on DNA damage-induced cancer cell death and anti-tumor immunity.
• Radioresistance in tumors is often caused by cell cycle heterogeneity and an immunosuppressive tumor microenvironment.
• Current RT strategies face limitations in overcoming these challenges.

Purpose of the Study:

• To develop and evaluate an ion generator-based strategy to enhance radiotherapy efficacy against radioresistant tumors.
• To investigate the mechanisms by which the ion generator modulates the tumor microenvironment and immune response.
• To assess the impact of this strategy on primary tumor growth and distant metastasis.

Main Methods:

• An ion generator was designed to degrade within the tumor microenvironment.
• The degradation products triggered iron-dependent ferroptosis, enhancing immunogenic cell death.
• Manganese-activated stimulator of interferon genes reversed the immunosuppressive environment.

Main Results:

• The strategy promoted dendritic cell maturation and enhanced CD8+ T cell infiltration.
• Intratumoral myeloid-derived suppressor cells were suppressed, and M2 macrophage polarization was limited.
• Significant inhibition of both primary and distal metastatic tumor growth was observed.

Conclusions:

• The ion generator strategy effectively creates an immunoreactive tumor microenvironment.
• This approach offers a robust method to overcome radioresistance and combat cancer metastasis.
• Potential for enhancing RT efficacy in clinically resistant tumors is high.