摘要目的:研究不同密度的肿瘤间质中肿瘤浸润淋巴细胞(TILs)对杭州标准肝细胞癌肝移植患者远期预后的影响。方法:本研究为回顾性队列研究，收集分析2018年1月—2023年12月首都医科大学附属北京朝阳医院肝胆外科符合杭州标准行同种异体肝移植术的83例肝细胞癌患者的临床资料，后运用苏木精-伊红染色研究肝移植切除病肝中TILs密度，根据其是否超过10%将其分为TILs阴性组(TILs<10%, n＝31)及TILs阳性组(TILs≥10%, n＝52)。分析其临床、病理特点，并对甲胎蛋白、TILs密度、微血管侵犯对于符合杭州标准肝细胞癌肝移植预后的意义进行研究。正态分布的计量资料以均数±标准差( ± s)表示，组间比较采用 t检验。非正态分布的计量资料以 M( Q1， Q3)表示，组间比较采用秩和检验。计数资料组间比较采用 χ2检验。同时运用Kaplan-Meier方法研究各个观察指标与总生存期关系并绘制生存曲线，应用Log-rank检验比较组间生存率差异，并采用多变量COX回归模型调整组间危险因素的分布。 结果:TILs阴性组术前甲胎蛋白为(15.69±1.21) U/mL，TILs阳性组术前甲胎蛋白为(12.17±0.13) U/mL，两者相比差异具有统计学意义( P<0.05)。TILs阴性组内微血管侵犯例数为8例，低分化、中分化、高分化级别肿瘤例数分别为8、23、0例，TILs阳性组微血管侵犯例数为3例，低分化、中分化、高分化级别肿瘤例数分别为2、31、19例，本研究结果显示TILs阴性组患者更容易发生肿瘤微血管侵犯，分化程度更差( P<0.05)。所有患者均定期随访，TILs阴性组和阳性组术后1、2、3年生存率分别为84.0%、77.6%、69.8%和94.7%、91.7%、86.6%( P<0.01)，通过COX多因素比例风险模型可知微血管侵犯( RR＝4.474, 95% CI：1.172～17.072, P＝0.028)、TILs阴性( RR＝5.081, 95% CI：1.420～18.184, P＝0.012)是影响杭州标准肝细胞癌肝移植患者远期预后的独立危险因素。 结论:符合杭州标准的肝细胞癌患者中，TILs密度与患者甲胎蛋白水平、肿瘤分化程度以及是否有微血管侵犯有关，TILs阴性提示患者预后较差。

abstractsObjective:To investigate the impact of Tumor-Infiltrating Lymphocytes (TILs) density in the tumor stroma on the long-term prognosis of hepatocellular carcinoma (HCC) liver transplant patients meeting the Hangzhou criteria.Methods:This study is a retrospective cohort study. The clinical data of 83 patients with hepatocellular carcinoma who met the Hangzhou criteria and underwent allogeneic liver transplantation from January 2018 to December 2023 in the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University were collected and analyzed. Hematoxylin and Eosin (HE) staining was used to study the density of TILs in the resected liver grafts. Patients were divided into TILs-negative group (TILs<10%, n=31) and TILs-positive group (TILs≥10%, n=52) based on whether the TILs density exceeded 10%. Clinical and pathological characteristics were analyzed, and the significance of alpha-fetoprotein (AFP), TILs density, and microvascular invasion on the prognosis of HCC patients who met the Hangzhou criteria was studied. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared between groups using t-test. Measurement data with skewed distribution were expressed as M ( Q1, Q3) and compared using rank-sum tests. Categorical data were compared using chi-square test. Kaplan-Meier method was used to study the relationship between various observation indicators and overall survival, and survival curves were plotted. Log-rank test was used to compare the survival rates between groups, and multivariate Cox regression model was used to adjust for the distribution of risk factors between groups. Results:The preoperative AFP level in the TILs-negative group was (15.69±1.21) U/mL, and in the TILs-positive group was (12.17±0.13) U/mL, with a statistically significant difference between the two groups ( P<0.05). In the TILs-negative group, 8 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 8, 23, and 0, respectively. In the TILs-positive group, 3 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 2, 31, and 19, respectively. The results indicated that patients in the TILs-negative group were more likely to have microvascular invasion and poorer tumor differentiation ( P<0.05). All patients were regularly followed up, and the 1-, 2-, and 3-year survival rates in the TILs-negative group and TILs-positive group were 84.0%, 77.6%, 69.8%, and 94.7%, 91.7%, 86.6%, respectively ( P<0.01). Cox proportional hazards model indicated that microvascular invasion ( RR=4.474, 95% CI: 1.172-17.072, P=0.028) and TILs-negative status ( RR=5.081, 95% CI: 1.420-18.184, P=0.012) were independent risk factors for the long-term prognosis of HCC patients who met the Hangzhou criteria. Conclusions:Among HCC patients meeting the Hangzhou criteria, the density of TILs in the tumor stroma is related to AFP levels, tumor differentiation, and the presence of microvascular invasion. TILs-negative status indicates a poorer prognosis for these patients.