Changes in and effects of Kupffer cells on residual tumor after cryoablation in rabbit hepatic VX2 tumor

Objective: 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 in vivo were studied. Methods: 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. Results: 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. Conclusion: 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.