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

PALACIOS, LUZ MARIA; VIANO, MARIA ESTEFANIA; GEYSELS, ROMINA CELESTE; NICOLA, JUAN PABLO; PELLIZAS, CLAUDIA; RODRIGUEZ-GALAN, MARIA CECILIA; FOZZATTI, LAURA

Congreso; XVIII Latin American Thyroid Society Congress; 2021

Tumor-Associated Macrophages Infiltration in a Xenograft Mouse Model ofAnaplastic Thyroid CancerLuz María Palacios, María Estefanía Viano, Romina Celeste Geysels, Juan Pablo Nicola, Claudia Pellizas, María Cecilia Rodríguez Galán and Laura FozzattiCentro de Investigaciones en Bioquímica Clínica e Inmunología. Consejo Nacional de Investigaciones Científicas y Técnicas. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba.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. Leucocyte infiltration in tumors was assessed via FACS 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% 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 andNKT cells) cells. We validated the clinical significance of the CD206 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 decreased survival in patients with ATC.Conclusion: Collectively, our data show the existence of a macrophage-enriched TME in ATC xenograft tumors, recapitulating ATC in humans. We believe that this mouse model will provide a powerful tool for investigating the importance of macrophages in therapeutic strategies against ATC.CHARACTER LIMIT: 2500 characters including spaces- 2178