OK-432联合PD-1单抗治疗肝癌射频消融后残存和远处转移瘤的机制及疗效研究

射频消融是当前临床上常用和有效的肝癌治疗手段之一。肝癌射频消融后肿瘤的复发和转移是一大难题。因此，有必要探索新的治疗策略去解决这一难题。OK-432是一种良好的抗肿瘤免疫激动剂。前期已有研究及我们预实验表明，OK-432可显著增强机体抗肿瘤免疫力，诱导CD8+T细胞向肿瘤内浸润。然而，免疫检查点的存在阻碍了CD8+T细胞对肿瘤的杀伤作用。免疫检查点抑制剂PD-1单抗目前已在临床上用于一些恶性肿瘤的治疗，其可以有效解除肿瘤细胞对T淋巴细胞的免疫抑制。基于此，本项目拟采用OK-432联合PD-1单抗治疗肝癌射频消融后的残存和远处转移瘤，向残存肿瘤内注入OK-432，增强机体抗肿瘤免疫力，促使CD8+T细胞向肿瘤内浸润，再联合使用PD-1单抗，解除肿瘤细胞对CD8+T细胞的免疫抑制，增强CD8+T细胞对肿瘤的杀伤作用，降低肝癌射频消融后肿瘤的复发和转移，具有重要的临床意义和良好的临床转化前景。

Radiofrequency ablation (RFA) is one of the most common and effective methods in the treatment of hepatocellular carcinoma (HCC) in clinical practice. The recurrence and metastasis of HCC after RFA is a difficult problem. Therefore, it is necessary to explore new treatment strategies to overcome it. OK-432 is a good anti-tumor immunostimulant. The previous studies and our preliminary experiments demonstrated that OK-432 can significantly enhance the anti-tumor immunity of the body and induce CD8 + T lymphocytes to infiltrate into the tumor. However, the presence of immunocheckpoint hinders the killing effect of CD8 + T lymphocytes on tumors. At present, PD-1 antibody has been used in clinic in the treatment of some malignant tumors. It can effectively relieve the immunosuppression of tumor cells to T lymphocytes. Based on these, this project plans to use the combination treatment of OK-432 with PD-1 monoclonal antibody to treat the residual tumor and distant metastasis of HCC after RFA. OK-432 was injected into the residual tumor to promote the infiltration of CD8+ T lymphocytes into the tumor, and then PD-1 monoclonal antibody was used to relieve the immunosuppression of the tumor cells to CD8 + T lymphocytes. It is to enhance the killing effect of CD8+ T lymphocytes on the tumors and reduce the recurrence and metastasis of HCC after RFA, which has an important clinical significance and a good prospect of clinical transformation.