Syngeneic N1-S1 Orthotopic Hepatocellular Carcinoma in Sprague Dawley Rat for the Development of Interventional Oncology-Based Immunotherapy: Survival Assay and Tumor Immune Microenvironment

SIMPLE SUMMARY: Interventional oncology (IO) approaches have been highly effective in treating hepatocellular carcinoma (HCC) locoregionally. Recently revealed anti-cancer immunity of IO-based immunotherapies proposed the promise of enhanced immunotherapy. However, the development of those therapies is still in its infancy with limited preclinical animal models. Preclinical animal models in IO-based immunotherapy research are the key resources to navigate the optimal procedure and efficacy of newly proposed IO-based immunotherapy approaches. ABSTRACT: Rodent HCC rat models provide advantages for interventional oncology (IO) based immunotherapy research compared to other established larger animal models or mice models. Rapid and predictable tumor growth and affordable costs permit the formation of a compelling preclinical model investigating novel IO catheter-directed therapies and local ablation therapies. Among orthotopic HCC models, the N1-S1 orthotopic HCC model has been involved in many research cases. Suboptimal tumor induction rates and potential spontaneous regression during tumor implantation procedures discouraged the use of the N1-S1 HCC model in IO-based immunotherapies. Here, N1-S1 HCC models were generated with a subcapsular implantation of two different number of N1-S1 cells using a mini-laporatomy. Tumor growth assay and immunological profiles which can preclinically evaluate the therapeutic efficacy of IO-based immunotherapy, were characterized. Finally, an N1-S1 HCC rat model generated with the proposed procedure demonstrated a representative immune suppressive HCC tumor environment without self-tumor regression. The optimized syngeneic N1-S1 HCC rat models represent an essential tool for pre-clinical evaluation of new IO immunotherapies for the treatment of HCC.