Does Heavy Ion Therapy Work Through the Immune System?

Combination of local therapies with immunotherapy, to convert the individual tumor into an in situ vaccine, is currently considered one of the most promising strategies to defeat cancer. The application of local radiation therapy as an adjuvant to immunotherapy is under active investigation both preclinically and clinically. The recent work of Gameiro et al published in the Red Journal in May this year as part of the Particle Therapy Special Issue (1) shows that protons can induce immunogenic modulation of the irradiated tissue, as already described with photons. Radiation induces both immune-stimulating and immune-suppressive pathways (2, 3). Photon radiation induces immunogenic cell death in a dose-dependent manner, by calreticulin translocation, High mobility group box 1, and adenosine triphosphate release (4). The complex balance between immunosuppressive and stimulatory effects can be shifted using a combination of immunotherapy. Sporadic observations of the abscopal effects in patients show that, if some of these immune suppressive pathways are counteracted, a systemic antitumor response can occur (2). Densely ionizing particle radiation may lead to a broader immunogenic response (5). Enhanced effectiveness in inducing nontargeted effects has been shown for high linear energy transfer radiation in 2-dimensional and 3-dimensional cell cultures (6). The experiments of