TUMOR-ASSOCIATED MACROPHAGES INFILTRATION IN A XENOGRAFT MOUSE MODEL OF ANAPLASTIC THYROID CANCER

EVENTO VIRTUAL

Congreso; XVIII Latin American Thyroid Congress; 2021

Sociedad Latinoamericana de Tiroides

Introduction: Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer. Characterized by its undifferentiated cells, itspreads quickly to distant organs and does not respond well to standardized therapy. Therefore, there is an urgent need to identify newbiological targets that can be translated into novel clinical approaches. Infiltration of macrophages in solid tumors is associated withpoor prognosis and this makes them attractive targets for anticancer therapy. Interestingly, ATC is densely infiltrated with macrophages,representing its potential as a therapeutic target. Objectives: We sought to study the main cellular components of the immune systemwithin the tumor microenvironment (TME) of ATC. Methods: A xenograft model of ATC was generated in SCID-NOD mice. TheATC cell line 8505c was subcutaneously inoculated into the right flank of mice. Leukocyte infiltration in tumors was assessed via flowcytometry analysis. Gene expression profiles were obtained from the NCBI Gene Expression Omnibus database and analyzed usingbioinformatics analysis. Results: A large amount of immune infiltrate was observed in ATC xenograft tumors. Tumors were comprisedof 2%-23% of CD45+ cells (leukocytes). Furthermore, 7%-9% of CD45+ cells were F4/80+, which revealed macrophages infiltrationinto the tumors. We further showed that 10%-40% of macrophages in ATC tumors were polarized toward a M2-like phenotype in theTME, as assessed by CD206 expression. In contrast, ATC tumors did not show the presence of CD3+ (T cells) or NK.1.1+ (NK andNKT cells) cells. We validated the clinical significance of CD206 expression in human ATC by analyzing public microarray datasets, andfound that the expression of CD206 was significantly higher in human ATC tissue samples than in normal thyroid tissues. In addition,high expression of CD206 was associated with a tendency towards decreased survival in patients with ATC. Conclusion: Collectively,our data show the existence of a macrophage-enriched TME in ATC xenografts, recapitulating ATC in humans. We believe that thismouse model will provide a powerful tool for investigating the importance of macrophages in novel therapeutic strategies against ATC.