An immunocompetent mouse model of liposarcoma

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Liposarcoma (LPS) is the most common soft tissue sarcoma, with subtypes ranging from low-grade well-differentiated LPS (WDLPS) to high-grade dedifferentiated LPS (DDLPS).
• DDLPS is associated with increased recurrence, metastasis, and poor response to current treatments.
• The absence of immunocompetent mouse models has hindered preclinical immunotherapeutic research for LPS.

Purpose of the Study:

• To establish a spontaneous, immunocompetent liposarcoma mouse model.
• To mimic human LPS signaling alterations for more relevant preclinical studies.
• To facilitate the development of novel immunotherapies for LPS.

Main Methods:

• Development of the ACPP mouse model through targeted deletion of Trp53 and Pten in adipocytes.
• Characterization of tumor subtypes (WDLPS, DDLPS, and mixed) arising in the ACPP model.
• Transcriptional profiling of murine and human DDLPS, and assessment of T cell infiltration.
• Generation and orthotopic injection of syngeneic cell lines derived from spontaneous ACPP DDLPS.

Main Results:

• The ACPP model spontaneously develops WDLPS and DDLPS, mirroring human disease.
• Murine and human DDLPS share transcriptional similarities, including altered expression of key oncogenes and tumor suppressors.
• Tumors in the ACPP model exhibit variable T cell infiltration, similar to human DDLPS.
• Derived syngeneic cell lines produce tumors with distinct growth and immune profiles.

Conclusions:

• The ACPP mouse model provides a valuable tool for studying liposarcoma immunobiology.
• This model enables more accurate preclinical testing of immunotherapeutics for LPS.
• Accelerated research using these models is expected to yield new therapeutic strategies for aggressive liposarcoma.