Macrophage-Tumor Crosstalk in the Pathogenesis of Follicular Thyroid Cancer

Abstract Thyroid cancer is the most common endocrine malignancy and one of fastest growing cancers in United States. Follicular thyroid carcinoma (FTC) represents second form diagnosed US often tied to mutations RAS protein family MAP kinase pathway. In addition driver mutations, FTC characterized by a unique tumor microenvironment (TME) composed cellular non-cellular components that impact tumorigenesis disease progression. Preliminary data from our lab has shown CD45+ immune cells account for approximately 68% all found whole tumors collected mouse models RAS-driven disease. Macrophages largest portion known cell populations. Further experiments have demonstrated lines isolated secrete cytokines recruitment activation state myeloid lineage, particularly macrophages. However, it’s unclear what type functional characteristics are induced these secreted factors how resulting macrophage phenotype affects Here, we sought determine bidirectional communication between macrophages could contribute development protumorigenic microenvironment. First, began defining affected previously unstimulated Through gene expression analysis encompassing several markers states, determined cell-secreted multiple genes associated with (TAM). particular, observed consistent upregulation IL-10 TNF-alpha, been worsening These results were further validated through quantification secretion. addition, role activated progression cancer, specifically effect macrophage-secreted on proliferation. direct indirect assays proliferation, classically-activated M1 inhibited Surprisingly, secretions alternatively-activated M2 reduced vitro growth some lines. proliferation was not death, but rather result delayed cycle. help define within model will identify potential therapeutic targets reduce activity