肝癌经皮微波凝固治疗前后局部免疫细胞浸润影响因素的分析

目的：探讨超声引导下经皮微波凝固疗法（PMCT）治疗肝癌前后影响患者局部免疫状态的因素。方法：78例经肝穿刺活检诊断的肝癌患者接受超声引导下PMCT治疗，于治疗前，后取肿瘤区组织，行免疫组化染色，观察部T淋巴细胞（CD3＋），自然杀伤细胞（CD56＋），巨噬细胞（CD68＋）浸润程度及增殖细胞核抗原（PCNA）阳性表达率，用多元回归方法分析免疫细胞浸润程度与患者临床临床参数间的关系。结果：PMCT治疗前患者肿瘤组织内3种免疫细胞均有不同程度的浸润，浸润程度与外周血甲胎蛋白（AFP）水平呈负相关（CD3＋：r=-0.075,P=0.049,CD56 :r=-0.062,P=0.041;CD68^ ;r=-0.007,P=0.035)，与癌结节大小呈负相关（CD3^ :r=-0.074,P=0.051;CD56^ :r=-0.100,P=0.12,CD68^ :r=-0.109,P=0.038)；与患者年龄，肝功能Child分级，肿瘤分化程度，癌结节数目均无相关性，治疗后治疗区组织3种免疫细胞的浸润程度均较治疗前明显增强（P＜0．01），并与治疗前免疫细胞的浸润程度呈正相关（CD3^ :r=0.256,P=0.005,CD56^ :r=0.257,P=0.002,CD68^ :r=0.275,P=0.001)。肿瘤细胞PCNA阳性表达率高处免疫细胞浸润少，细胞凝固坏死，PCNA表达阴性但细胞结构尚可见处，免疫细胞浸润程度较高；肿瘤细胞坏死呈无结构处无免疫细胞浸润。结论：肝癌PMCT治疗前，后患者局部免疫细胞浸润程度分别受血AFP水平和肿瘤存活程度的影响。PMCT原位完全灭活肿瘤是治疗后局部免疫细胞浸润增加的前提，治疗前调整患者基础免疫状态至较好水平，对提高治疗后局部免疫应答有益。

Influencing factors of local immunocyte infiltration in hepatocellular carcinoma tissues pre- and post-percutaneous microwave coagulation therapy

Objective To investigate the influencing factors of the local immunity in tissues of hepatocellular carcinoma (HCC) before and after percutaneous microwave coagulation therapy (PMCT). Methods Seventy eight patients with HCC diagnosed by needle biopsy of liver underwent PMCT. Before the treatment and three and 17 days after the treatment specimens of carcinoma tissues were obtained by ultrasound guided liver biopsy. The extents of infiltration of CD3 + cell, natural killer cells (CD56 +), and macrophages (CD68 +), and the expression rate of proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry. The relation between the extents of immunocyte infiltration and the clinical parameters was analyzed with multiple regression. Results Before PMCT infiltration of the three kinds of immunocytes was found in the carcinoma tissues to different degrees with a great variation among individuals. A remarkable increase in the extent of infiltration of the three kinds of immunocytes was found three days after the treatment and continued or remained till the 17th post PMCT day( P <0 01). The post PMCT extent of immunocyte infiltration was positively correlated with the pre PMCT extent (CD3 +: r =0 256, P =0 005; CD56 +: r =0 257, P =0 002; CD68 +: r =0 275, P =0 001). A negative correlation was found between the extent of immunocyte infiltration and serum alpha fetal protein (AFP) and between the extent of immunocyte infiltration and tumor size (for serum AFP, CD3 +: r = -0 075, P =0 049; CD56 +: r =-0 062, P =0 041; CD68 +: r =-0 007, P =0 035; for tumor size, CD3 +: r =-0 074, P =0 051; CD56 +: r =-0 100, P =0 012; CD68 +: r =-0 109, P =0 038). No correlation was found between the extent of immunocyte infiltration and age of patient, Child Pugh class of tumor, grade of tumor differentiation, and number of tumor. The extent of immunocyte infiltration was lesser in the carcinoma tissues with higher expression rate of PCNA. The extent of immunocyte infiltration was greater in the carcinoma tissues where PCNA expression was negative and carcinoma cells had necrotized but with their structure recognizable. No immunocyte infiltration was found in the necrotic and structureless tumor tissues. Conclusion The local immunocyte infiltration in patients with HCC was influenced by serum AFP and the grade of tumor cell necrosis pre and post PMCT. Destruction of tumor tissue in situs by PMCT is the premise of increase of immunocyte infiltration. Before PMCT improving the immune status of the patients helps enhance the local immune response.