Immunomodulatory effects of targeted radionuclide therapy

Abstract

It is now clear that conventional radiation therapy can reinstate cell death immunogenicity. Recent preclinical data indicate that targeted radionuclide therapy that irradiate tumors at continuous low dose rate also can elicit immunostimulatory effects and represents a promising strategy to circumvent immune checkpoint inhibitor resistance. In this perspective, we discuss the accumulating preclinical and clinical data suggesting that activation of the immune system through the cGAS-STING axis and the release of extracellular vesicles by irradiated cells, participate to this antitumor immunity. This should need to be considered for adapting clinical practices to state of the art of the radiobiology and to increase targeted radionuclide therapy effectiveness.

Keywords: Exosomes; ICD; Microvesicles; Radioimmunotherapy; Radiopharmaceuticals; Type I interferon; cGAS-STING.