原发性肝癌射频治疗后局部免疫功能的变化及其临床意义

Effects on local immunological functions after radiofrequency ablation for primary hepatocellular carcinoma

目的对原发性肝癌(hepatocellu lar carc inom a,HCC)射频消融治疗(rad iofrequency ab lation,RFA)前后肿瘤内部及边缘热休克蛋白70(heat shock prote in,HSP70)的表达、CD8+T细胞数量的变化以及RFA治疗后,肿瘤边缘HSP70表达与肿瘤边缘CD8+T细胞数量之间的关系进行观察,探讨RFA治疗对原发性肝癌局部免疫功能状态的影响及其可能的临床意义。方法对17例HCC分别在RFA治疗前、后1个月,于肿瘤内部和肿瘤边缘超声引导下穿刺活检取样;采用PowerV isionTM二步染色法进行免疫组化分析,测定HSP70的表达、CD8+T细胞的数量;随访HCC复发/新生情况。结果RFA治疗后肿瘤边缘组织HSP70表达增强(Z=3.337,P=0.001)、CD8+T细胞数量增多(Z=1.996,P=0.049);RFA治疗后,≤4 cm肿瘤组的占位边缘CD8+T细胞数量高于>4 cm肿瘤组(Z=1.966,P=0.048)。RFA治疗后,边缘组织HSP70表达与CD8+T细胞数量之间呈正相关关系(r=0.489,P=0.046);RFA治疗后,无复发或新生组的占位边缘组织HSP70表达和CD8+T细胞数量分别高于复发或新生组(Z=2.009,P=0.045;Z=2.007,P=0.045)。结论RFA治疗后边缘HSP70表达增强、CD8+T细胞数量增多,显示RFA治疗后局部免疫原性提高,抗肿瘤效应细胞浸润增加。

Objective To investigate effects on local immunological functions and their clinical significances after radiofrequency ablation （RFA） for primary hepatocellular carcinoma （HCC）. Methods A total of 17 cases of primary HCC was included in the study. Ultrasound-guided puncture and biopsy was carried out before and after RFA for tumor sampling inside and at the border of the RFA sphere, respectively. The expression of heat shock protein 70 （HSP70） and the number of CD8^＋ T cell in situ were analyzed with immunohistochemistry using the PowerVision Two-Step Detection System. Follow-up examinations were conducted for detecting tumor relapse or recurrence. Results Following the RFA, significantly up-regulated expression of HSP70 （Z = 3.337, P = 0.001） and increased number of CD8^＋ T cells （Z = 1.996, P = 0.049） were seen at the border zone of RFA sphere. The number of CD8^＋ T cells was significantly higher in tumors ≤4 cm in diameter than those 〉4 cm in diameter （Z = 1.966, P = 0.048）. A positive relation was seen between HSP70 expression and CD8^＋ T cell number at the border zone of RFA sphere （r = 0.489, P = 0.046）. The HSP70 expression and the CD8^＋ T cell number at the border zone of RFA sphere were higher in recurrence-free patients than in recurrent patients, respectively （Z = 2.009, P = 0.045; Z = 2.007, P = 0.045）. Conclusions Following the RFA, the HSP70 expression and the CD8^＋ T cell number at the border zone of RFA sphere will be elevated, indicating that RFA induces an immune response against tumor antigens and a tumor-specific T cell reaction.