Prognostic value of CD28⁻CD57⁺CD8⁺ T cells for early immunotherapy response in hepatocellular carcinoma: a prospective observational study.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally. The atezolizumab plus bevacizumab ("T + A") regimen is the first-line treatment for unresectable HCC, but predictive biomarkers are lacking. Immunosenescence is linked to tumor immune evasion and treatment resistance. To evaluate whether baseline peripheral blood CD28⁻CD57⁺CD8⁺ T-cell proportion predicts early response to "T + A" therapy in HCC. Thirty-two newly diagnosed HCC patients receiving "T + A" were enrolled. Treatment response was assessed after 3 to 4 cycles of therapy using mRECIST criteria. CD28⁻CD57⁺CD8⁺ T-cell proportions were quantified by flow cytometry. Predictive performance was evaluated using receiver operating characteristic(ROC) analysis, and predictors were identified via logistic regression. Non-responders had significantly higher baseline CD28⁻CD57⁺CD8⁺ T-cell levels than responders (p = 0.0269). ROC analysis yielded an AUC of 0.730 (95% CI: 0.541-0.919) for predicting non-response. The optimal cutoff was 29.05%, with 66.70% sensitivity and 85.70% specificity. Logistic regression confirmed it as an independent risk factor (OR = 1.146, p = 0.027). The baseline CD28⁻CD57⁺CD8⁺ T-cell proportion predicts early response to "T + A" therapy in HCC and may serve as a biomarker for treatment resistance.