Prognostic Value of the Ratio of Interleukin-2 and Interleukin-10 in Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Therapy

Introduction Despite the advent of anti-PD-1 immunotherapy as a promising treatment for HCC, there remains a significant gap in the comprehensive analysis of peripheral blood immunological markers that could predict treatment response. This study aims to identify peripheral blood immunological markers predictive of anti-PD-1 therapy response in HCC patients to improve clinical outcomes. Methods We retrospectively analyzed 69 HCC patients treated with anti–PD-1 therapy, divided into a training cohort ( n = 30) and a validation cohort ( n = 39). Clinical characteristics, hematological indices, cytokine levels, and serum PD-1 were assessed. Logistic regression and ROC curve analyses were performed to evaluate prognostic value, with bootstrap validation to assess model robustness. In addition, tumor samples from 6 patients underwent WES, and bioinformatic analyses were conducted to explore mutational profiles and their associations with immune infiltration as supportive mechanistic validation. Results The IL-2/IL-10 ratio was significantly associated with tumor progression after adjustment for covariates (OR 2.918, 95% CI 1.191-7.150, p = 0.019) and achieved superior predictive performance (AUC 0.884, 95% CI 0.766-1.000) compared with conventional inflammation-based scores. Bootstrap validation confirmed model stability (corrected AUC ≈ 0.88), and external validation supported predictive value. Whole-exome sequencing revealed that mutations in genes such as FLT3, TET2, and IDH2 were commonly present in HCC. Immune infiltration analyses indicated that these mutations were associated with increased Treg and decreased Th1 infiltration, consistent with the clinical trend. Additional analyses of public transcriptomic datasets further supported these observations. Conclusion Our study reveals that a low IL-2/IL-10 ratio is significantly associated with adverse prognosis in HCC patients and may serve as a practical and biologically relevant biomarker for predicting the efficacy of anti–PD-1 therapy. Moreover, systematic evaluation of immune status could provide important guidance for predicting immunotherapy efficacy and supporting future clinical decision-making in HCC management.