Abstract:

 Objective To elucidate the relationship between preoperative immunotherapy，the abundance of tertiary lymphoid structures（TLS）in hepatocellular carcinoma（HCC）tissues，and to evaluate patient prognosis following liver transplantation. Methods The clinical data of 149 liver transplant patients with liver cancer at Huashan Hospital Affiliated to Fudan University from January 2018 to December 2023 were retrospectively analyzed. Pathological slides of each patient were scored for TLS. Patients were categorized into four groups based on downstaging treatment outcomes ：those initially meeting the Milan criteria（n ＝ 35），those exceeding the Milan criteria without downstaging treatment（n ＝ 38），successful downstaging cases（n ＝ 33），and unsuccessful downstaging cases （n ＝ 43）. Kaplan-Meier analysis and the log-rank test were employed for survival analysis. The correlation betweenimmunotherapy and TLS abundance was assessed using non-parametric statistical methods. Results Survival analysis of the overall cohort revealed that patients with high intratumoral TLS abundance had significantly higher recurrence-free survival（RFS）than those with low TLS abundance（P ＜ 0.05）. Among patients receiving downstaging treatment，the recurrence risk in the successful downstaging group was significantly lower than in the unsuccessful group（P ＜ 0.05）. Non-parametric testing of the successful downstaging group demonstrated that preoperative immunotherapy significantly increased intratumoral TLS abundance（P ＜ 0.05）. Similarly，nonparametric testing of all patients receiving immunotherapy showed a statistically significant increase in intratumoral TLS abundance in the successful downstaging group（P ＜ 0.05）. Conclusion Successful downstaging withpreoperative immunotherapy improves the prognosis of HCC patients undergoing liver transplantation，potentially by enhancing intratumoral TLS abundance. 

Key words:

Hepatocellular carcinoma, Liver transplantation, Immunotherapy, Tertiary lymphoid structures

摘要：

目的 明确肝移植术前免疫治疗与肝癌组织三级淋巴结构（tertiary lymphoid structures，TLS）丰度及预后的关系。方法 回顾性分析 2018 年 1 月至 2023 年 12 月复旦大学附属华山医院肝脏移植中心149 例肝癌肝移植患者临床资料。对每例患者的病理切片进行 TLS 评分。依据降期治疗情况将患者分为 4 组：初始符合米兰标准组（35 例），超出米兰标准无降期治疗组（38 例），降期成功组（33 例），降期未成功组（43 例）。采用 Kaplan-Meier 法和 Log-rank 检验进行生存分析。使用非参数检验的方法验证免疫治疗与 TLS 之间的相关性。 结果 对整体队列进行生存分析后发现，瘤内 TLS 丰度高的患者，其无复发生存率（recurrence-free survival，RFS）显著高于瘤内 TLS 丰度低的患者（P ＜ 0.05），对所有接受降期治疗患者进行生存分析后发现，降期成功组复发风险明显低于降期未成功组（P ＜ 0.05）。对降期成功组进行两独立样本非参数检验后发现，术前免疫治疗会显著影响瘤内 TLS 丰度，具有统计学差异（P ＜ 0.05）。对所有接受免疫治疗患者行两独立样本非参数检验后发现，降期成功组瘤内 TLS 丰度明显增高，具有统计学差异（P ＜ 0.05）。结论 术前免疫治疗降期成功可改善肝癌肝移植患者的生存预后，其机制可能是术前免疫治疗能增加肝癌患者瘤内 TLS 丰度。 

关键词:

癌 , 肝移植 , 免疫治疗 , 三级淋巴结构