Targeted immunotherapy and tumor immunogenicity in liver transplant recipients: A study on lenvatinib and PD-L1 inhibition

Background: Long-term immunosuppression from transplants which reduces the body’s ability to detect and fight the tumor, is the main reason hepatocellular carcinoma (HCC) often recurs. Objectives: This study evaluates the ability of lenvatinib (used to manage angiogenesis) and an anti-PD-L1 agent to help treat recurrent or new liver cancer in patients who have undergone LT. Methods: Participants of this retrospective cohort study included 15 people who had received a transplant and were treated with low-dose tacrolimus, 8–12 mg of lenvatinib and atezolizumab delivered through a vein every three weeks. Clinical data collected were overall survival (OS), progression-free survival (PFS), ORR, instances of tumor recurrence and events of adverse reactions related to treatment. Flow cytometry, Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to estimate the presence of CD8+ T cells, Tregs (Treg) and cytokine levels in tissues. Results: The data showed that the median OS was 36 months, almost twice as high as the data from sorafenib and the PFS time was 12 months, also substantially higher. At 12 months, 60% of patients improved by at least 50% in their scan (13.3% were free from disease while 46.7% improved) and the disease returned only in 20% of patients. Analysis found higher numbers of CD8+ T-cells in tumors (p=0.004), lower Treg cell numbers (p=0.008), increased IFN-? and TNF-? and decreased IL-10. At the same time, there was a sharp decline in circulating tumor DNA (ctDNA) which followed decrease in imaging abnormalities. Severe acute rejection of the graft did not occur; adverse effects from therapy were addressed. Conclusion: This combination shows promising effects and good safety in patients with HCC who have received liver transplants. Such a method offers a fresh choice for treating those who are thought not to be suitable for immunotherapy, so it needs to be tested in more extensive controlled research.