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

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

Congreso; XVIII Latin American Thyroid Society Congress 2021; 2021

Latin American Thyroid Society LATS

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 InvestigacionesCientíficas 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. Characterizedby its undifferentiated cells, it spreads quickly to distant organs and does not respond well tostandardized therapy. Therefore, there is an urgent need to identify new biological targets that canbe translated into novel clinical approaches. Infiltration of macrophages in solid tumors is associatedwith 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 thetumor microenvironment (TME) of ATC.Methods: A xenograft model of ATC was generated in SCID-NOD mice. The ATC cell line 8505c wassubcutaneously inoculated into the right flank of mice. Leucocyte infiltration in tumors was assessedvia FACS analysis. Gene expression profiles were obtained from the NCBI Gene Expression Omnibusdatabase and analyzed using bioinformatics analysis.Results: A large amount of immune infiltrate was observed in ATC xenograft tumors. Tumors werecomprised of 2-23% CD45+cells (leukocytes). Furthermore, 7-9% of CD45+cells were F4/80+, whichrevealed macrophages infiltration into the tumors. We further showed that 10-40% of macrophagesin ATC tumors were polarized toward a M2-like phenotype in the TME, as assessed by CD206expression. 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 publicmicroarray datasets, and found that the expression of CD206 was significantly higher in human ATCtissue samples than in normal thyroid tissues. In addition, high expression of CD206 was associatedwith decreased survival in patients with ATC.Conclusion: Collectively, our data show the existence of a macrophage-enriched TME in ATCxenograft tumors, recapitulating ATC in humans. We believe that this mouse model will provide apowerful tool for investigating the importance of macrophages in therapeutic strategies againstATC.