射频消融(Radiofrequency ablation, RFA)常常导致中大型和不规则肿瘤的不完全消融。为了解决这一临床问题，我们提出了一种新的治疗策略，即将OK-432与抗程序性细胞死亡蛋白1 (αPD-1)抗体结合，用于不完全RFA (iRFA)后残留肿瘤的肝细胞癌(HCC)治疗。我们在体外评估了OK-432对未成熟树突状细胞(iDCs)的影响。采用CCK-8试剂盒和ELISPOT评估了OK-432诱导的CD8+T细胞与αPD-1抗体在Hepa1-6细胞上的杀伤效应。我们发现，OK-432显著提高了DCs的成熟水平，而OK-432诱导的CD8+T细胞与αPD-1抗体的联合应用显著增强了CD8+T细胞的功能。在体内实验中，我们治疗了HCC模型小鼠，分别给予(1)伪iRFA+磷酸盐缓冲液(PBS)； (2)iRFA+PBS； (3)iRFA+OK-432； (4)iRFA+αPD-1； 或(5)iRFA+OK-432+αPD-1。我们发现，OK-432与αPD-1抗体的联合治疗显著增加了CD8+T细胞的浸润和功能，并显著减少了iRFA后残留肿瘤中FoxP3+调节性T细胞的数量。此外，与其他四组相比，三种联合治疗组(iRFA+OK-432+αPD-1抗体)显示出最小的肿瘤体积和最长的生存时间。OK-432与αPD-1抗体的联合治疗引发了强烈的抗肿瘤免疫反应，显著抑制了iRFA后HCC的残留肿瘤。该概念可能为增强射频消融治疗中大型和不规则HCC的治疗效果提供了新的治疗策略。本研究的数据可根据合理请求从对应作者处获取。版权所有 ©2023该作者。由Elsevier Masson SAS出版。保留所有权利。

Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC).The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8+ T cells in combination with an αPD-1 antibody on Hepa1-6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8+ T cells in combination with αPD-1 antibody significantly enhanced the function of CD8+ T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8+ T cells and significantly decreased the number of FoxP3+ regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups.The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs.The data of this study are available from the corresponding author on reasonable request.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.