INTRODUCTION: The treatment algorithm of advanced hepatocellular carcinoma (HCC) 
has evolved since the introduction of immunotherapy. The IMbrave150 trial set 
atezolizumab-bevacizumab as a new standard-of-care first-line treatment for 
unresectable HCC patients. However, for patients with intermediate or advanced 
stage with portal vein thrombosis but without distant metastases, 90Yttrium 
transarterial radioembolization (90Y-TARE) is considered the treatment of 
choice.
AREAS COVERED: We discuss the main evidence regarding the use of 90Y-TARE in 
HCC, the recent progress of immunotherapy in this tumor, and the preclinical 
rationale of combining VEGF blockade with the other two treatment strategies.
EXPERT OPINION: HCC has an extremely heterogeneous tumor immune 
microenvironment. This may explain the inconsistent outcomes obtained with 
immune-checkpoint inhibitors. The identification of patients who could benefit 
most from immunotherapy is crucial; however, reliable markers of response are 
lacking. Radiation therapy and VEGF inhibition have an established synergism 
with immunotherapy, mainly linked to enhanced antigen presentation and reduced 
immunosuppressive immune infiltrate. Combining an immune-checkpoint inhibitor 
with VEGF blockade and 90Y-TARE might hence overcome primary resistances 
observed when each of these treatments is administerd alone.