The availability of these systemic drugs has raised the feasibility of combinations with radiotherapy. In particular, over recent years, increasing evidence has supported the rationale of combining radiotherapy with immunotherapy for earlier stages of the disease. The unique characteristics of radiotherapy offer the great potential to boost immunothera­peutic responses in patients. These include induction of immunogenic cell death, supporting a pro-inammatory tumor microenvironment and increased availability of tumor antigen [95]. In brief, radiotherapy has the potential to sup­port the conversion of an immunologically “cold” tumor into an immunologically “hot” tumor [96]. Radiotherapy has also been shown to upregulate PD-L1 expression in vivo and combination of radiation with anti-PD-L1 treatment led to signicantly increased survival in a murine HCC mouse model [97]. In a rst clinical case study of ve patients treated with SBRT followed by anti-PD1 antibody treatment, two patients showed complete response, while three patients had partial responses according to modied RECIST criteria. The one-year LC and OS rates were both 100% [98]. These results are in line with a report by Yu and colleagues, who observed signicantly longer PFS and OS in patients with previous or concurrent radiotherapy during application of nivolumab for advanced HCC [99]. To further enhance syn­ergy of radiotherapy and ICB approaches with triple­combinational treatments are also under evaluation. In a preclinical study by Sheng and colleagues, authors reported further improvement of survival of tumor bearing mice after adding an ATR inhibitor (AZD6738) to radioimmunotherapy (radiation + αPD-L1) [100].