Anti-tumour immunity induced after alpha irradiation

Radioimmunotherapy (RIT) is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses beta-emitting radioisotopes, but recently a growing interest has emerged for the clinical development of alpha particles. Alpha emitters are ideal for killing isolated or small clusters of tumour cells, thanks to their specific characteristics (high linear energy transfer (LET) and short path in the tissue), and their effect is less dependent on dose rate, tissue oxygenation or cell cycle status than gamma and X-rays. Several studies have been performed to describe alpha emitter radiobiology and cell death mechanisms induced after alpha irradiation. But so far, no investigation has been undertaken to analyze the impact of alpha particles on the immune system, when several studies have shown that external irradiation, using gamma and X-rays can foster an antitumour immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 (213Bi) irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective anti-tumour response that is mediated by tumour specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that 213Bi treated MC-38 cells release "danger signals" and activate dendritic cells. Our results demonstrate that alpha irradiation can stimulate adaptive immunity, elicits an efficient anti-tumour protection and therefore is an immunogenic cell death (ICD) inducer, which provides an attractive complement to its direct cytolytic effect on tumour cells.

GORIN J;  MENAGER J;  GOUARD S.;  MAUREL C;  GUILLOUX Yannick;  FAIVRE-CHAUVET A;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  CHEREL M.;  DAVODEAU F;  GASCHET J; 

2014-07-28

NEOPLASIA PRESS

JRC85525

1522-8002,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC85525,   

10.1016/j.neo.2014.04.002,