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Updated: Sep 24, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Dynamic proteomic change of tumor and immune organs in an immune-competent hepatocellular carcinoma mouse model
Jiaqi Jiao1, Linlin Ji2, Xianju Li1
1State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics Beijing 102206, China.
Abstract:
Subcutaneous implantation of a human cancer cell line in immune-deficient mice (CDX) is a commonly used tool in preclinical studies for the assessment of potential anti-cancer drugs. As immunotherapy is transforming cancer treatment, tumor models in immunocompetent mice are necessary for us to understand the immune aspects of tumor biology. However, the systemic immune response to the implantation of cancer cells at proteome level is unclear. In this study, we characterized the dynamic proteomic changes of subcutaneous tumors and 5 immune organs (draining lymph node, mesenteric lymph node, spleen, thymus and marrow) at six time points after implantation using a Hepa1-6 derived allograft mouse model. Our data suggest that interaction of the implanted tumor cells with mouse immune system followed the trajectory of "tumor rejection" to "immune evasion" in that the tumor gained the ability to evade the immune system for growth. Furthermore, anti-PDL2 antibody was validated here as an optional immunotherapy strategy to inhibit the growth of Hepa1-6 subcutaneous tumors. These findings from our study provided valuable information for the understanding of tumor and immune interaction and shed light on the rational design for clinical cancer treatment and other preclinical experiments.
Insights
This study reveals how tumors evade the immune system in immunocompetent mice, transitioning from rejection to evasion. Anti-PDL2 antibody therapy showed potential in inhibiting tumor growth, offering insights for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Proteomics
Background:
- Subcutaneous cancer cell implantation in immune-deficient mice (CDX models) is standard for preclinical drug testing.
- Immunotherapy's rise necessitates tumor models in immunocompetent mice to study immune interactions.
- The systemic proteomic response to implanted cancer cells in immunocompetent hosts remains poorly understood.
Purpose of the Study:
- To characterize dynamic proteomic changes in tumors and immune organs after cancer cell implantation in immunocompetent mice.
- To elucidate the trajectory of tumor-immune system interaction.
- To validate anti-PDL2 antibody as a potential immunotherapy.
Main Methods:
- Utilized a Hepa1-6 derived allograft mouse model.
- Implanted cancer cells subcutaneously.
- Analyzed proteomic changes in tumors and five immune organs (draining lymph node, mesenteric lymph node, spleen, thymus, marrow) at six time points.
Main Results:
- Tumor-immune system interaction followed a path from initial rejection to eventual immune evasion.
- Tumors acquired the ability to evade the immune system, facilitating their growth.
- Anti-PDL2 antibody demonstrated efficacy in inhibiting Hepa1-6 subcutaneous tumor growth.
Conclusions:
- The study provides valuable insights into tumor-immune interactions in immunocompetent hosts.
- Findings support the 'tumor rejection to immune evasion' trajectory.
- Results inform the rational design of preclinical experiments and clinical cancer immunotherapies.
