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Published on: April 22, 2019
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Immunocompetent Murine Models Recapitulate the Heterogeneous Tumor-Immune Microenvironment of Human Liposarcoma
Amanda M Shafer1, Emma Kenna2,3, Lexi-Ann F Golden2
1Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Summary
Researchers developed a new immunocompetent mouse model for dedifferentiated liposarcoma (DDLPS), a rare cancer. This model and its derived cell lines will accelerate the discovery of new therapies for this aggressive soft tissue sarcoma.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Liposarcoma is the most common soft tissue sarcoma, with dedifferentiated liposarcoma (DDLPS) being an aggressive subtype.
- Current understanding and treatment options for liposarcoma, particularly DDLPS, are limited, highlighting a need for advanced research models.
- The progression from well-differentiated liposarcoma to DDLPS involves complex signaling alterations and increased metastatic potential.
Purpose of the Study:
- To develop a novel, autochthonous, immunocompetent genetically engineered mouse model for liposarcoma.
- To create a preclinical platform that accurately mimics human liposarcoma, including its histological and transcriptional features.
- To generate syngeneic cell lines from the liposarcoma model for further in-depth immunobiological and therapeutic studies.
Main Methods:
- Development of the ACPP (AAV8-Ap2.2-eGFP/Cre Ptenf/f;Trp53f/f C57BL/6) mouse model via targeted Cre-mediated deletion of Trp53 and Pten in adipocytes.
- Histological and transcriptional characterization of tumors developed in the ACPP model.
- Establishment and evaluation of syngeneic DDLPS cell lines derived from ACPP tumors, assessing their in vivo tumor formation, growth dynamics, and immune composition.
Main Results:
- The ACPP model successfully recapitulates human liposarcoma, developing well-differentiated liposarcoma, DDLPS, and mixed tumors.
- Murine and human DDLPS tumors exhibit shared key transcriptional features and heterogeneous T-cell infiltration.
- ACPP-derived syngeneic DDLPS cell lines reliably form tumors with distinct growth kinetics, aggressiveness, and immune profiles.
Conclusions:
- The ACPP mouse model offers a clinically relevant platform for studying liposarcoma in an immunocompetent setting.
- The model and derived cell lines are valuable tools for understanding liposarcoma immunobiology and molecular mechanisms.
- This platform is expected to accelerate preclinical studies and the development of novel therapies for liposarcoma patients.
