Debate on immunotherapy for recurrence of liver cancer after transplantation

Liver cancer is the second most common cause of cancer death in the world. New liver cancer patients in China account for more than half of the worlds liver cancer every year. In the whole treatment process of liver cancer, the commonly used treatment methods mainly include hepatectomy, liver transplantation, liver ablation, targeted therapy, immunotherapy, interventional therapy and so on.

Liver transplantation is one of the radical methods of liver cancer, but the 5-year survival rate of liver cancer recipients is less than 50%. Postoperative recurrence and metastasis is the main reason affecting the long-term survival of liver cancer recipients. At present, immunotherapy represented by PD-1 / PD-L1 immune checkpoint inhibitors has achieved significant efficacy in the treatment of advanced liver cancer. However, there are many disputes about whether immunotherapy can be used for the recurrence of liver cancer after transplantation. Because patients after liver transplantation need to use immunosuppressive drugs routinely, acute rejection may be caused when immunosuppressive drugs and antitumor immunotherapy are used at the same time. So how to try to use immunotherapy to fight tumor without causing rejection? 

Tumor immunotherapy is to kill tumor cells by strengthening the surveillance and killing ability of the immune system and correcting the imbalance of the immune microenvironment. At present, PD-1 / PD-L1 inhibitors and CTLA-4 inhibitors are commonly used in the immunotherapy of liver cancer. Studies have shown that CTLA-4 and PD-1 play a role in transplantation immune tolerance. CTLA-4 mainly plays a role in the induction period of immune tolerance, while PD-1 plays a role in the maintenance period of immune tolerance. A study included 35 patients who used immunotherapy after liver transplantation. The study found that the expression levels of PD-1 on the surface of CD8 + T cells and CD4 + T cells in patients without acute rejection were higher than those in patients with acute rejection, suggesting that the expression of PD-1 plays an important role in maintaining immune tolerance of liver transplantation.

Previous studies have shown that the incidence of acute rejection is high when immunotherapy is applied to patients with tumor recurrence after liver transplantation. Therefore, it is considered that immunotherapy should be used with special caution for patients with recurrence after liver transplantation. However, in the real world, there have been many successful application cases. Case reports tell us that it is possible to use antitumor immunotherapy for patients with recurrence after liver cancer transplantation.    

As for how to avoid the rejection of anti-tumor immunotherapy as much as possible, some studies summarized 39 patients after solid organ transplantation, 16 patients had rejection, 5 patients had immunohistochemical detection of PD-L1, and 4 patients were positive for graft PD-L1 / PD-1. It is suggested that PD-1 / PD-L1 positive can predict the occurrence of rejection. Therefore, it is suggested that liver transplantation biopsy should be performed routinely before immunotherapy for patients with recurrence after liver transplantation. If PD-L1 is positive, CTLA-4 inhibitor can be considered for treatment. Of course, some studies have pointed out that in order to avoid the rejection caused by immunotherapy in patients with recurrence of liver cancer after liver transplantation, the preventive application of high-dose glucocorticoid therapy does not affect the therapeutic effect of patients. 

Therefore, for the immunotherapy of patients with recurrence of liver cancer after liver transplantation, we must carefully screen the cases and formulate an individualized treatment plan. In the process of treatment, we should closely observe the changes of liver function and the occurrence of rejection.

 

Cindy