Tumor Purity in Preclinical Mouse Tumor Models

Tumor biology is determined not only by immortal cancer cells but also its tumor microenvironment consisted of non-cancerous cells and extracellular matrix, together they dictate pathogenesis and response to treatments. Tumor purity is the proportion of cancer cells in a tumor. It is a fundamental property of cancer and is associated with many clinical features and outcomes. Here we report the first systematic study of tumor purity in patient-derived xenograft (PDX) and syngeneic tumor models using NGS data for tumors. We found that PDX models possess cancer-specific tumor purity that mimics patient tumors, with great difference in stromal content and immune infiltration, and is affected by the immune systems of host mice. Human stroma in a tumor is completely replaced by mouse stroma after the initial engraftment in mice, tumor purity is then stable in subsequent transplantations and increases only slightly by passage. Similarly, tumor purity is an intrinsic property of syngeneic models with cancer specificity. Computational and pathology analysis revealed the impact on tumor purity by the diverse stromal and immune profiles. Our study deepens the understanding of mouse tumor models that will help better and novel uses of them on developing cancer therapeutics, especially ones targeting tumor microenvironment.Tumor purity is the proportion of cancer cells in tumor. It is a fundamental property of cancer and is associated with many clinical features and outcomes. Here we report the first systematic study of tumor purity in patient-derived xenograft (PDX) and syngeneic tumor models using NGS data for >9,000 tumors. We found that PDX models possess cancer-specific tumor purity that mimics patient tumors, with great difference in stromal content and immune infiltration, and is affected by host mouse immune system. Human stroma is completely replaced by mouse stroma after the initial engraftment of human tumor in mouse. Tumor purity is then stable with slight increases during passaging. Similarly, tumor purity in syngeneic models is cancer specific with unique stromal and immune profiles. Our study deepens the understanding of mouse tumor models that will help better and novel uses of them on developing cancer therapeutics, especially ones targeting tumor microenvironment.