Do Tumor Cells or the Tumor Microenvironment Determine the Phenotype of Tumor-Associated Macrophages?

Tumor-associated macrophages (TAMs) create an immunosuppressive tumor microenvironment (TME) that will promote tumor progression. The goal of this project is to understand whether the pattern of TAMs in a tumor is determined by the tumor cells or by the host tissue environment. Knowing how the phenotype of TAMs is determined will help us better target TAMs to improve cancer patient’s outcome. Moreover, another goal of this project is to understand whether the TAMs that develop in a primary tumor have the same phenotype as those that develop in subsequent metastases. Comparing gene expression profiles between TAMs in different tissues can provide future directions to improve cancer therapies so that we can better target TAMs in order to effectively eradicate primary and metastatic tumors. Using flow cytometry to examine like tumors growing in different tissues, we found that subcutaneous, orthotopic, and intravenous LLC tumor models all have similar TAM profiles that are distinct from genetically engineered CC10Cre KrasG12D p53-/- spontaneous lung tumor models. In addition, using single-cell sequencing to investigate the PyMT primary mammary gland tumors and metastatic lung tumor the and CC10Cre KrasG12D p53-/- spontaneous lung tumors, we can conclude that the TAM profile of the primary tumor and subsequent metastasized tumor have similar TAM profiles. As a result, we can conclude that the TAM profile is dependent on the tumor cells themselves instead of the microenvironment.