Characterizing hepatocellular carcinoma stem markers and their corresponding susceptibility to NK-cell based immunotherapy

• DOI: 10.3389/fimmu.2023.1284669
• Publication Date: 2023-10-26T13:45:44Z
• Authors: Jason Chiang; Po-Chun Chen; Janet Pham; Cat-Quynh Nguyen; Kawaljit Kaur; Steven S. Raman; Anahid Jewett
• Keywords: HCCS; Stem cell marker

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and fourth-leading cause of all cancer-related deaths around world. Liver transplantation, surgery, local ablation are curative therapies for early-stage HCC. However, post-treatment outcomes can vary based on histopathologic stage. Poorly-differentiated HCC associated with higher rates tumor progression lower overall survival compared to well-differentiated after therapy. In this study, we aimed characterize stem cell (CSC) profile histopathologically-proven well poorly-differentiated HCCs in an in-vitro environment. We characterized stem-like each type their surface markers susceptibility NK cell-mediated cytotoxicity.Flow cytometry was used quantify differential expression MHC-class I, CD54, CD44 between well- HCCs. Primary untreated cells, IL-2 stimulated supercharged (sNK) cytotoxicity assessed against IFN-γ supernatant from respective experimental arm also induce differentiation Finally, temporal effector using real-time quantitative analysis imaging impedance (eSight study).Poorly-differentiated demonstrated low I high CD44. Treatment cells secreted or cytokine induced comparison were more susceptible sNK cells. significantly IL-2-stimulated These findings recapitulated analysis.Poorly-differentiated found have marker patterns CSCs, making them highly cell-based immunotherapy. NK-cell therapy potentially be leveraged as a neoadjuvant adjuvant Supercharged which rapidly expanded therapeutic levels, uniquely capable lysing both poorly- This finding suggests that not only exhibit enhanced features cells' targets but activating T MHC class I.