Tumor-Associated Macrophages Infiltration in a Xenograft Mouse Model of Anaplastic Thyroid Cancer

PALACIOS, LUZ MARIA; NICOLA, JUAN PABLO; FOZZATTI, LAURA; GEYSELS ROMINA; RODRÍGUEZ GALÁN, MARÍA CECILIA ; VIANO, ESTEFANIA; PELLIZAS, CLAUDIA GABRIELA

Virtual

Congreso; XVIII Congreso de la Sociedad Latinoamericana de Tiroides; 2021

Latin American Thyroid Society

Introduction: Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer. Characterized by its undifferentiated cells, it spreads quickly to distant organs and does not respond well to standardized therapy. Therefore, there is an urgent need to identify new biological targets that can be translated into novel clinical approaches. Infiltration of macrophages in solid tumors is associated with poor 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 system within the tumor microenvironment (TME) of ATC.Methods: A xenograft model of ATC was generated in SCID-NOD mice. The ATC cell line 8505c was subcutaneously inoculated into the right flank of mice. Leukocyte infiltration in tumors was assessed via flow cytometry analysis. Gene expression profiles were obtained from the NCBI Gene Expression Omnibus database and analyzed using bioinformatics analysis.Results: A large amount of immune infiltrate was observed in ATC xenograft tumors. Tumors were comprised of 2-23% of CD45+ cells (leukocytes). Furthermore, 7-9% of CD45+ cells were F4/80+, which revealed macrophages infiltration into the tumors. We further showed that 10-40% of macrophages in ATC tumors were polarized toward a M2-like phenotype in the TME, as assessed by CD206 expression. In contrast, ATC tumors did not show the presence of CD3+ (T cells) or NK.1.1+ (NK and NKT cells) cells. We validated the clinical significance of CD206 expression in human ATC by analyzing public microarray datasets, and found 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 this mouse model will provide a powerful tool for investigating the importance of macrophages in novel therapeutic strategies against ATC.