T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma

•In patients with HCC, exhausted T cells and CD103+ tissue-resident memory T cells have opposing roles.•Enrichment of poorly functional PD-1+ exhausted T cells in the tumor tissue is associated with poor progression-free survival.•Tissue-resident memory T cells have higher effector function and metabolic activity and are associated with longer survival.•The balance between CD103+ tissue-resident and exhausted T cells can predict outcomes during PD-1 therapy.