Yi Fengtao, Liu Lei, Ding Menglan, Zhu Yaling, Song Qingling, Zeng Ceng
Department of Oncology, General Hospital of Central Theater Command of Chinese People's Liberation Army No. 627 Wuluo Road, Wuchang District, Wuhan 430070, Hubei, P. R. China.
Int J Clin Exp Pathol. 2021 Jan 1;14(1):75-85. eCollection 2021.
Cryoablation can directly kill tumor cells through sudden changes in temperature. It can also enhance lymphocyte function and cause distant tumor regression far from the ablation treatment area. In order to further explore the changes of immune function after cryoablation, the changes of Kupffer cells (KCs), the main immune cells in the liver, and their effects on untreated tumors were studied.
Rabbit VX2 liver cancer models were constructed. The growth of liver tumors was confirmed by ultrasound after transplantation for 3 weeks. Fifteen Japanese white rabbits were divided into a tumor control group and cryoablation group. Cryoablation group was treated with cryoablation of a single or partial tumor. Histologic and immunohistochemical changes of the treatment area and untreated tumor area before and after cryoablation were observed, and the phagocytic function changes of KCs around the untreated area and treatment area were observed by electron microscopy.
Cryoablation areas showed necrosis, infiltration of inflammatory cells (including KCs), and fibrosis of tissue. The number of inflammatory cells in the unfrozen tumor area was increased in the same treated rabbit. There was a significant difference in the maximum diameter of unfrozen tumors between the frozen group and control group at 15th days after cryoablation (P<0.05), while the difference was not obvious at the 3rd and 7th day (P>0.05). Electron microscopy showed that the number of debris fragments engulfed by KCs around the tumor after cryoablation was significantly higher than that of the control group. In the same rabbit, we compared the amount of debris between tissue surrounding the unfrozen area and around the cryoablation area. There was a significant difference on the 3rd day after cryoablation, P=0.043, while there was no significant difference on the 7th day, P=0.348.
After cryoablation, inflammatory cells aggregated around the cryoablated area. The activity of KCs had been increased and the function of phagocytosis enhanced. KCs had a certain inhibitory effect on the untreated tumor in the same animal at the early stage (within 15 days), but it was not enough to restrain the growth of the untreated tumors.
冷冻消融可通过温度的突然变化直接杀死肿瘤细胞。它还能增强淋巴细胞功能并导致远离消融治疗区域的远处肿瘤消退。为了进一步探究冷冻消融后免疫功能的变化,研究了肝脏主要免疫细胞库普弗细胞(KCs)的变化及其对未治疗肿瘤的影响。
构建兔VX2肝癌模型。移植3周后通过超声确认肝肿瘤的生长情况。15只日本白兔分为肿瘤对照组和冷冻消融组。冷冻消融组对单个或部分肿瘤进行冷冻消融治疗。观察冷冻消融前后治疗区域和未治疗肿瘤区域的组织学和免疫组化变化,并通过电子显微镜观察未治疗区域和治疗区域周围KCs的吞噬功能变化。
冷冻消融区域显示坏死、炎性细胞(包括KCs)浸润及组织纤维化。同一治疗兔未冷冻肿瘤区域的炎性细胞数量增加。冷冻消融后第15天,冷冻组与对照组未冷冻肿瘤的最大直径差异有统计学意义(P<0.05),而第3天和第7天差异不明显(P>0.05)。电子显微镜显示,冷冻消融后肿瘤周围被KCs吞噬的碎片数量明显高于对照组。在同一只兔中,比较未冷冻区域和冷冻消融区域周围组织的碎片量。冷冻消融后第3天差异有统计学意义,P=0.043,而第7天差异无统计学意义,P=0.348。
冷冻消融后,炎性细胞聚集在冷冻消融区域周围。KCs的活性增强,吞噬功能提高。KCs在早期(15天内)对同一动物体内未治疗的肿瘤有一定抑制作用,但不足以抑制未治疗肿瘤的生长。