NICOLA JUAN PABLO
Congresos y reuniones científicas
Título:
Infiltration of Tumor-Associated Macrophages in a Xenograft Mouse Model of Anaplastic Thyroid Cancer
Autor/es:
PALACIOS, LM; VIANO, ME; GEYSELS, RC; NICOLA, JP; PELLIZAS, CG; RODRIGUEZ GALAN, MC; FOZZATTI, L
Reunión:
Congreso; XVIII Latin American Thyroid Congress; 2021
Institución organizadora:
Latin American Thyroid Society
Resumen:
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.
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.
