Our study aims to evaluate the benefit of the administration of immunotherapy (atezolizumab), in patients with hepatocellular carcinoma (HCC), prior surgical resection of the tumor.
HCC is the most prevalent primary liver cancer, responsible for nearly 800,000 deaths annually, making it the third leading cause of cancer-related mortality worldwide. Ablation by radiologic micro-waves or surgical resection represent at the moment the only curative therapies for early stages of the disease. Despite these curative options, HCC recurrence is frequent.
Recently, immunotherapy has demonstrated good results on patient overall survival for advanced stages of HCC in comparison to sorafenib. Because of the beneficial effect of immunotherapy on HCC, several groups have attempt to use it as adjuvant therapy in order to reduce the recurrence rate. However the results are at the moment controversial. One can hypothetize that postoperative inflammation and liver regeneration can negatively impact the effect of the immunotherapy. Therefore, the administration of the treatmeent before surgical resection could overcome this issue.
All adult patients undergoing liver resection for HCC at the Geneva University Hospitals (HUG), with prior informed and signed consent.
Patients of childbearing age must be willing to use a contraception at the day of inclusion and for at least 5 months after the last infusion.
Negative pregnancy test at inclusion
Patients will require to be eligible for surgical resection according to the BCLC guidelines (very early to early stage with preserved liver function and good patient condition) (4).
Patients who do not ultimately undergo liver resection due to unforeseen reasons (this happens rarely, such as in the presence of unexpected HCC progression discovered during surgery).
Patients with an ongoing pregnancy (an unlikely event, as non-surgical HCC treatments would be prioritized in such cases).
Patients unable to follow procedures due to language barriers, insufficient comprehension of project language, or unable to give consent.
Patients <18 years.
Parallel
Atezolizumab
DrugPatients will receive two doses of atzolizumab 6 and 3 weeks before surgery
Difference in frequency of flow cytometry-assessed HCC-specific CD8+ cells in the periphery (PBMC) between patients with vs without ICI therapy prior to liver surgery
We will assess the impact of ICI therapy on the frequency of HCC-specific CD8+ lymphocytes. The currently recruited patients will be compared to historical patients without ICI treatment. After flow cytometry sorting, bulk RNA sequencing of CD8+ cells will be performed. The SEQTR method will define the frequency of HCC-specific TCR.
Tumor microenvironment changes induced by ICI therapy
Especially changes in HCC-specific T cell response in the periphery after versus prior to surgery. TCR subtypes will be identified by TCR single cell sequencing in the peripheral blood and in the tumor. Additionnaly immune cell type population, their activation and suppression markers as well as the frequency of the subtypes will be assesed by flow cytometry (CD8, CD4, memory T cells, exhausted markers (PD-L1, TIM-3, LAG-2)).
Overall survival and recurrence free survival
We will analyze the survival and recurrence rates in order to evaluate the impact or potential benefit of neoadjuvant atezolizumab
Tumor burden
We will evaluate the impact of atezolizumab on the tumor burden such as the number and size of HCC nodules and compare it before the treatment and before surgery to evaluate the level of downstaging of the tumor that we can expect.
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