Artículo

Soldati, R.; Berger, E.; Zenclussen, A.C.; Jorch, G.; Lode, H.N.; Salatino, M.; Rabinovich, G.A.; Fest, S. "Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments" (2012) International Journal of Cancer. 131(5):1131-1141
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Abstract:

The immunosuppressive strategies devised by neuroblastoma (NB), the most common solid extracranial childhood cancer, are poorly understood. Here, we identified an immunoevasive program triggered by NB through secretion of galectin-1 (Gal-1), a multifunctional glycan-binding protein. Human and mouse NB cells express and secrete Gal-1, which negatively regulates T cell and dendritic cell function. When injected subcutaneously in syngeneic A/J mice, knockdown transfectants expressing low amounts of Gal-1 (NXS2/L) showed reduction of primary tumor growth by 83-90% and prevented spontaneous liver metastases in contrast to NXS2 cell variants (NXS2/H, NXS2 wildtype) expressing high amounts of Gal-1. Splenocytes from mice receiving Gal-1 knockdown NXS2/L cells secreted higher amounts of IFN-c and displayed enhanced cytotoxic T-cell function compared to NXS2/H or NXS2 controls. Immunohistochemical analysis revealed a six- to tenfold increase in the frequency of CD4+ and CD8+ T cells infiltrating tumors from mice receiving knockdown transfectants. This effect was confirmed by in vitro migration assays. Finally, supernatants of NXS2/H or NXS2 cells suppressed dendritic cell (DC) maturation and induce T cell apoptosis, whereas these effects were only marginal on DCs and T cells exposed to supernatants from NXS2/L cells. These results demonstrate a novel immunoinhibitory role of the Gal-1-glycan axis in NB, highlighting an alternative target for novel immunotherapeutic modalities. © 2011 UICC.

Registro:

Documento: Artículo
Título:Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments
Autor:Soldati, R.; Berger, E.; Zenclussen, A.C.; Jorch, G.; Lode, H.N.; Salatino, M.; Rabinovich, G.A.; Fest, S.
Filiación:Department of Pediatrics, Medical Faculty, Otto-von Guericke University of Magdeburg, Germany
Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von Guericke University of Magdeburg, Germany
Department of Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von Guericke University of Magdeburg, Germany
Department of Pediatric Oncology, University Medicine Greifswald, Greifswald, Germany
Laboratorio de Inmunopatología, Instituto de Biología Y Medicina Experimental, IBYME-CONICET, Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:, tolerance; Dendritic cells; Galectin-1; Neuroblastoma; T cells; galectin 1; gamma interferon; animal cell; animal experiment; animal model; apoptosis; article; cancer inhibition; CD4+ T lymphocyte; CD8+ T lymphocyte; cell function; cell maturation; cell transfer; controlled study; cytotoxic T lymphocyte; dendritic cell; female; flow cytometry; gene silencing; human; human cell; immunohistochemistry; immunomodulation; immunoregulation; in vitro study; liver metastasis; lymphocyte migration; male; metastasis inhibition; mouse; neuroblastoma; nonhuman; priority journal; protein expression; protein secretion; T lymphocyte; tumor escape; Animals; Antigen-Presenting Cells; Apoptosis; Blotting, Western; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Movement; Cell Proliferation; Dendritic Cells; Female; Flow Cytometry; Galectin 1; Genetic Therapy; Humans; Immunoenzyme Techniques; Interferon-gamma; Lung Neoplasms; Mice; Mice, Inbred A; Neuroblastoma; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured
Año:2012
Volumen:131
Número:5
Página de inicio:1131
Página de fin:1141
DOI: http://dx.doi.org/10.1002/ijc.26498
Título revista:International Journal of Cancer
Título revista abreviado:Int. J. Cancer
ISSN:00207136
CODEN:IJCNA
CAS:galectin 1, 258495-34-0; gamma interferon, 82115-62-6; Galectin 1; Interferon-gamma, 82115-62-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00207136_v131_n5_p1131_Soldati

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Citas:

---------- APA ----------
Soldati, R., Berger, E., Zenclussen, A.C., Jorch, G., Lode, H.N., Salatino, M., Rabinovich, G.A.,..., Fest, S. (2012) . Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments. International Journal of Cancer, 131(5), 1131-1141.
http://dx.doi.org/10.1002/ijc.26498
---------- CHICAGO ----------
Soldati, R., Berger, E., Zenclussen, A.C., Jorch, G., Lode, H.N., Salatino, M., et al. "Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments" . International Journal of Cancer 131, no. 5 (2012) : 1131-1141.
http://dx.doi.org/10.1002/ijc.26498
---------- MLA ----------
Soldati, R., Berger, E., Zenclussen, A.C., Jorch, G., Lode, H.N., Salatino, M., et al. "Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments" . International Journal of Cancer, vol. 131, no. 5, 2012, pp. 1131-1141.
http://dx.doi.org/10.1002/ijc.26498
---------- VANCOUVER ----------
Soldati, R., Berger, E., Zenclussen, A.C., Jorch, G., Lode, H.N., Salatino, M., et al. Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments. Int. J. Cancer. 2012;131(5):1131-1141.
http://dx.doi.org/10.1002/ijc.26498