Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)
Abstract
Purpose : Cancer cells produce innate immune signals following detection of radiation-induced cytosolic DNA via signaling pathways such as cGAS-STING. High linear energy transfer (LET) radiations induce more DNA double-strand breaks (DSBs) per unit dose than low-LET radiations, potentially enhancing immunogenic effects. This work explores the in vitro dose response characteristics of pro-immunogenic interferon-beta (IFN b ) and cGAS-STING antagonist three-prime repair exonuclease 1 (TREX1) from varying-LET radiations. Methods : IFN b and TREX1 expression were measured in MCC13 cells irradiated with graded doses of x-rays or fast neutrons (comparable LET to carbon-12) via ELISA, immunofluorescence, and qPCR assays. Laboratory measurement of the RBE for IFN b production (RBE IFN b ) and TREX1 upregulation (RBE TREX1 ) was compared to the modeled RBE for DSB induction (RBE DSB ) from Monte Carlo DNA damage simulations. RBE IFN b models were applied to radiation transport simulations to quantify the potential secretion of IFN b from representative proton, helium-4, and carbon-12 beams. Results : Maximum IFN b secretions occurred at 5.7 Gy and 14.0 Gy for neutrons and x-rays, respectively (RBE IFN b of 2.5). TREX1 signal increased linearly, with a four-fold higher upregulation per unit dose for fast neutrons (RBE TREX1 of 4.0). Monte Carlo modeling suggests an enhanced Bragg peak-to-entrance ratio for IFNb production in charged particle beams. Conclusion : High-LET radiation…
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