Evaluation of the tumoricidal efficacy of adoptive cell transfer using hepatocellular carcinoma-derived organoids.

Background: Tumor-derived organoid, namely tumoroid, can realistically retain the clinicopathologic features of original tumors even after long-term in vitro expansion. Here we develop this production methodology derived from hepatocellular carcinoma primary samples and generate a platform to evaluate the tumoricidal efficacy of autologous adoptive cell transfer including tumor infiltrating lymphocytes and peripheral blood lymphocytes.
Methods: Haematoxylin and eosin together with immunohistochemistry staining were employed to ascertain the morphologic and histological features of tumoroids and original tumors. Tumor killing ability of T cells was detected by lactate dehydrogenase assay and propidium iodide staining. In tumoroid xenograft mouse model, tumor volumes were measured and T cell functions were examined by flow cytometry technique.
Results: Four tumoroids with characteristics of poor differentiation and mild fibrosis were successfully established from fourteen hepatocellular carcinoma samples. More robust antitumor potential and hyper-functional phenotype of all four tumor infiltrating lymphocytes were observed compared to matched peripheral blood lymphocytes in coculture system. In tumoroid xenograft mouse models, however, only one patient-derived tumor infiltrating lymphocytes with the highest antitumor activity can bestow efficient tumor eradication. Conclusions: Hepatocellular carcinoma tumoroid-based models could represent invaluable resources for evaluating the tumoricidal efficacy of autologous adoptive cell transfer. Tumor infiltrating lymphocytes should be a promising and yet-to-be-developed regimen to treat hepatocellular carcinoma. 2022 Journal of Gastrointestinal Oncology. All rights reserved.