A recent spatial transcriptomic study involving HCC patients receiving anti-PD-1 therapy revealed a distinct tumor-immune barrier structure comprising SPP1+ macrophages and CAFs localized at tumor boundaries in non-responders (19), interestingly, HMGB2+ HCC cells were enriched around the tumor-immune barrier in non-responders (19), yet the role of HMGB2 in the immunotherapy resistance microenvironment of HCC was not investigated. This evidence concerns the gene HMGB2 and neoplasm.