Resumen
Stereotactic ablative radiotherapy (SABR), which irradiates tumors with high-dose radiation per fraction, promotes anti-tumor immunity by stimulating various immune processes. SABR also induces vascular damage and obstructs blood flow, thereby increasing tumor hypoxia and upregulation of hypoxia-inducible factors HIF-1a and HIF-2a, master transcription factors for the cellular response to hypoxia. HIF-1a and HIF-2a are key players in the upregulation of immune suppression in hypoxia. Therefore, the radiation-induced increase in anti-tumor immunity is masked by the HIF-mediated immune suppression. Pre-clinical experiments show that inhibition of HIF-1a effectively prevents immune suppression and improves anti-tumor immunity. A combination of HIF-1a inhibitors with immunotherapy with checkpoint blocking antibodies may represent a novel approach to boost anti-tumor immunity and enhance the efficacy of SABR.