Tumor Purity in Preclinical Mouse Tumor Models.

Area of Science:

• Oncology
• Cancer Biology
• Translational Research

Background:

• Tumor biology involves cancer cells and the tumor microenvironment, influencing disease progression and treatment response.
• Tumor purity, the fraction of cancer cells, is a key factor linked to clinical features and outcomes.
• Mouse tumor models are crucial for cancer research but require thorough characterization.

Purpose of the Study:

• To systematically investigate tumor purity in patient-derived xenograft (PDX) and syngeneic tumor models.
• To understand the factors influencing tumor purity, including host-related and intrinsic properties.
• To enhance the utility of mouse models for cancer therapeutics development, particularly those targeting the tumor microenvironment.

Main Methods:

• Analysis of next-generation sequencing data from over 9,000 PDX and syngeneic tumors across 27 and 19 cancer types, respectively.
• Computational and pathological analysis to assess stromal and immune cell infiltration.
• Characterization of tumor purity stability across serial transplantations in PDX models.

Main Results:

• Tumor purity in PDX models is cancer-specific and mirrors patient tumors, with host immune systems modulating stromal and immune content.
• Human stroma in PDX models is rapidly replaced by mouse stroma, with purity remaining stable post-engraftment and through passages.
• Syngeneic models also exhibit intrinsic, model- and cancer-specific tumor purity, influenced by stromal and immune profiles.

Conclusions:

• Tumor purity is an intrinsic property of PDX and syngeneic models, offering reliable platforms for cancer research.
• Understanding tumor purity and microenvironment dynamics in these models is vital for advancing cancer drug development.
• This study provides a comprehensive resource for optimizing the use of mouse models in preclinical cancer studies.