CELL INTELLIGENCE · 肿瘤细胞治疗研究

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) shows heterogeneous responses to treatment with immune checkpoint inhibitors, and predictive biomarkers for dual immune checkpoint blockade remain insufficiently defined. The STRIDE regimen, combining tremelimumab and durvalumab, improves the survival of patients with unresectable HCC, but a substantial proportion of patients experience early progression. We investigated whether pretreatment intratumoral CD8 + tumor-infiltrating lymphocyte (TIL) density was associated with treatment response and progression-free survival (PFS) in patients treated with STRIDE. PATIENTS AND METHODS: This retrospective, single-center study included 26 consecutive patients with unresectable HCC who received STRIDE and underwent pretreatment liver tumor biopsy. CD8 + TIL density was assessed using immunohistochemistry. Tumors were classified as CD8-high or CD8-low using a prespecified cutoff (15.9 cells/high-power field). RESULTS: Fifteen patients were classified as CD8-high and 11 as CD8-low. The objective response rate was significantly higher in the CD8-high group than in the CD8-low group (60.0% vs . 9.1%, p =0.005). The median PFS was significantly longer in the CD8-high group [8.8 months, 95% confidence interval (CI)=3.0-24.5] than in the CD8-low group (2.0 months, 95%CI=0.8-7.2; p =0.019). The frequency of grade 2 immune-related adverse events did not differ significantly between groups. CONCLUSION: Pretreatment intratumoral CD8 + TIL density was associated with an improved response and a longer PFS in STRIDE-treated HCC. Baseline tumor immune contexture may serve as a practical predictive biomarker for STRIDE. These findings are exploratory and hypothesis-generating, and require validation in larger prospective studies.