Proportion of TIM-1+ Bregs was elevated in tumours compared to peri-tumoural regions and blood of cancer patients, and positively correlated with disease progression, early recurrence, and invasion. TIM-1+ Breg frequency was negatively correlated to overall survival and limited proliferation and function of CD8+ effector T cells. TIM-1+ Bregs facilitated immune escape in HCC via novel exosomal HMGB1-TLR2/4-MAPK pathways. This evidence concerns the gene HMGB1 and cancer.