RESUMO
Interferons (IFNs) play an important role in tumor-immune system interactions. As one of the main mediators of IFNs, myxovirus resistance A (MxA) is upregulated in various cancers. However, the exact role of MxA in breast cancer is not fully understood. As part of the immune response to tumors, tumor-infiltrating lymphocytes (TILs) have prognostic significance in breast cancer. The aim of our present study was to examine the relationship between MxA and immune system components, including the amount of TILs and human leukocyte antigen (HLA) expression, in breast cancer. TILs, MxA expression, HLA intensity, and clinicopathological factors were retrospectively analyzed in 688 patients with primary breast cancer between 1993 and 1998 and in 705 patients with triple-negative breast cancer (TNBC) between 2004 and 2011. MxA expression was higher in TNBC tumors than in other subtypes. High MxA levels were associated with a higher histologic grade, abundant TILs, and stronger HLA-ABC expression in both the TNBC subtype within the consecutive breast cancer cohort and the validation TNBC cohort. MxA expression showed a significant positive correlation with TILs, the number of CD8(+) cells, and the number of CD69(+) cells in the validation TNBC cohort. High MxA levels and abundant TILs were found to be independent prognostic factors for disease-free survival in patients with TNBC. These results indicate that MxA expression is closely related to TILs in TNBC and, along with TILs, provides prognostic information after chemotherapy in patients with TNBC.
Assuntos
Linfócitos do Interstício Tumoral/patologia , Proteínas de Resistência a Myxovirus/metabolismo , Análise Serial de Tecidos/métodos , Neoplasias de Mama Triplo Negativas/patologia , Regulação para Cima , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Lectinas Tipo C/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
BACKGROUND: The neural crest (NC) is a multipotent embryonic cell population, which is induced by an integration of secreted signals including BMP, Wnt, and FGF and, subsequently, NC cell fates are specified by a regulatory network of specific transcription factors. This study was undertaken to identify a role of Sp5 transcription factor in vertebrates. RESULTS: Xenopus Sp5 is expressed in the prospective neural crest regions from gastrulation through the tadpole stages in early development. Knockdown of Sp5 caused severe defects in craniofacial cartilage, pigmentation, and dorsal fin. Gain- and loss-of-function of Sp5 led to up- and down-regulation of the expression of NC markers in the neural fold, respectively. In contrast, Sp5 had no effect on neural induction and patterning. Sp5 regulated the expression of neural plate border (NPB) specifiers, Msx1 and Pax3, and these regulatory factors recovered the expression of NC marker in the Sp5-deficient embryos. Depletion of Sp5 impaired NC induction by Wnt/ß-catenin or FGF signal, whereas its co-expression rescued NC markers in embryos in which either signal was blocked. CONCLUSIONS: These results suggest that Sp5 functions as a critical early factor in the genetic cascade to regulate NC induction downstream of Wnt and FGF pathways.