Differential Immune Modulation With Carbon-Ion Versus Photon Therapy.

Area of Science:

• Radiation oncology
• Immunology
• Cancer research

Background:

• Radiation therapy (RT) impacts tumor microenvironment (TME) immunity.
• The differential immunomodulatory effects of various RT types remain unclear.

Purpose of the Study:

• To compare the immunomodulatory effects of carbon-ion therapy (CiRT) versus photon therapy (PhRT) on solid tumors.
• To investigate RT-induced changes in TME immune cell populations and cytokine profiles.

Main Methods:

• Orthotopic 4T1 mammary tumors in immunocompetent hosts were treated with CiRT or equivalent doses of PhRT.
• TME immune characteristics were quantified using flow cytometry and multiplex cytokine analysis 72 hours post-RT.

Main Results:

• PhRT decreased CD4+ and CD8+ T cells, while CiRT did not significantly alter CD8+ T-cell infiltration.
• High-dose CiRT elevated pro-inflammatory cytokines (granzyme B, IL-2, TNF-α) from CD8+ T cells; PhRT increased IFN-γ.
• PhRT increased regulatory T cell proliferation at most doses, whereas high-dose CiRT also induced this effect.

Conclusions:

• Low-dose CiRT is lymphocyte-sparing compared to PhRT.
• High-dose CiRT is a potent inducer of pro-inflammatory cytokines in the TME.
• CiRT warrants further investigation for its potential to modulate TME immunologic characteristics.