ICOS and hepatocellular carcinoma: This notion is best exemplified by (i) a study of Di Blasi et al. showing that the presence of certain TIL clusters (e.g., ICOS+ TIGIT+ CD4+ TILs) can serve as a prognostic indicator for the response to checkpoint blockade therapy [108]; and by (ii) the improved progression-free survival of HCC patients treated with Atezolizumab (blocking PD-1 checkpoint pathway) in combination with the VEGF-blocking antibody Bevacizumab (blocking VEGF) that has recently been approved as first line therapy in HCC [34].