KEY POINTS
- This preclinical study tested Eclipse radiotherapy, which delivers low-dose radiotherapy to the whole gross tumor volume and stereotactic body radiotherapy to selected intratumoral subvolumes; combined with anti-programmed death 1, the authors termed the approach immuno-Eclipse radiotherapy.
- Mouse bulky tumor models included CT26 colon carcinoma, Lewis lung carcinoma, and B16-OVA melanoma, with tumors approximately 400–900 mm³ before treatment.
- The fractionated regimen delivered 10 Gy × 3 to the stereotactic body radiotherapy subvolume and 2 Gy × 3 to the whole tumor, combined with anti-programmed death 1.
- In the bulky CT26 model, immuno-Eclipse radiotherapy produced a 27.3% cure rate (3 of 11 mice), which was not observed with low-dose radiotherapy plus anti-programmed death 1 or partial stereotactic body radiotherapy plus anti-programmed death 1.
- Mechanistic experiments supported an interferon type I / natural killer cell / dendritic cell / cytotoxic T-cell axis, with reduced efficacy after natural killer cell depletion, cytotoxic T-cell depletion, interferon receptor blockade, XCL1 neutralization, or extracellular vesicle inhibition.
CLINICAL TAKEAWAY
This is an interesting adaptive immunoradiotherapy concept for bulky tumors: low-dose radiotherapy may inflame the broader tumor microenvironment while a stereotactic body radiotherapy boost drives antigen release and innate immune activation. But the evidence here is preclinical, not practice-changing. The authors note ongoing phase 1 clinical evaluation, so this should be read as mechanistic rationale for clinical testing rather than a treatment approach ready for routine use.