自然杀伤细胞在原发性肝细胞肝癌中的浸润及其与预后的关系

Prognostic significance of natural killer cell infiltration in hepatocellular carcinoma

背景与目的:对某些实体瘤研究显示肿瘤高浸润自然杀伤细胞(naturalkiller cell,NK cell)与癌症患者良好的预后相关。本研究探讨NK细胞在肝癌组织中的浸润分布及对肝细胞肝癌(hepatocellular carcinoma,HCC)患者生存和预后的影响。方法:应用流式细胞术检测肝癌切除组织中浸润的NK细胞的比例,并进一步应用免疫组化方法证实原位CD56+细胞的分布特点,同时比较CD56+细胞浸润密度与肝癌患者生存的关系。结果:肿瘤组织浸润淋巴细胞(tumor-infiltrating lymphocytes,TIL)中NK细胞的比例是(11.8±8.1)%,显著低于周围非肿瘤组织浸润淋巴细胞(nontumor-infiltrating lymphocytes,NIL)中的比例(18.0±7.9)%(P=0.002);组织原位观察癌巢CD56+细胞为(2.3±2.6)细胞/视野,也是显著少于癌旁组织的(8.5±4.5)细胞/视野(P<0.001)。癌巢NK细胞浸润密度低组患者患者的无瘤生存率(P=0.027)及总体生存率(P=0.005)明显低于浸润密度高组,而癌旁NK细胞浸润密度对二者无影响。多因素分析显示,癌巢NK细胞浸润密度是影响生存的独立预后因素(HR=2.658,P=0.019)。结论:HCC患者癌巢NK细胞浸润减少,其低密度浸润提示预后不良。

Background and Objective：Several studies have Shown the correlation of high numbers of tumor-infiltrating natural killer （NK） cells with a good prognosis for cancer patients. This study was to investigate the impact of NK cell infiltration on the survival and prognosis of patients with hepatocellular carcinoma （HCC） after resection. Methods： The proportion of infiltrating NK cells of HCC patients was measured using flow cytometry, and the expression of CD56＋ （NK） cells was investigated using immunohistochemistry. Prognostic values of intratumoral and peritumoral NK cell densities were evaluated by Kaplan-Meier method and Cox regression. Results： The level of NK cells was significantly lower in tumor-infiltrating lymphocytes （TIL） of HCC patients than in nontumor-infiltrating lymphocytes （NIL） [（11.8 ± 8.1）% vs. （18.0±7.9）%, P= 0.0023. The density of NK cells was also significantly lower in cancer nests than in peritumoral lesions （2.3 ± 2.6 vs. 8.5 ± 4.5 cells per field, P〈0.001）. Patients with low intratumoral NK cells had shorter disease-free survival （P= 0.027） and overall survival （P=0.005） than patients with high intratumoral NK cells. In contrast, NK cells in the peritumoral area showed no prognostic significance for either disease-free survival or overall survival. Multivariate Cox proportional hazards analysis showed that intratumoral NK cell density was an independent prognostic fator of prolonged overall survival （hazard ratio = 2.658, P=0.019）. Conclusion= Low NK cells infiltration could predict poor prognosis in patients with HCC.