Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments
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...
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00207136_v131_n5_p1131_Soldati http://hdl.handle.net/20.500.12110/paper_00207136_v131_n5_p1131_Soldati |
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paper:paper_00207136_v131_n5_p1131_Soldati2023-06-08T14:41:21Z Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments Salatino, Mariana , 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 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. Fil:Salatino, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00207136_v131_n5_p1131_Soldati http://hdl.handle.net/20.500.12110/paper_00207136_v131_n5_p1131_Soldati |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
, 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 |
| spellingShingle |
, 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 Salatino, Mariana Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments |
| topic_facet |
, 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 |
| description |
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. |
| author |
Salatino, Mariana |
| author_facet |
Salatino, Mariana |
| author_sort |
Salatino, Mariana |
| title |
Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments |
| title_short |
Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments |
| title_full |
Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments |
| title_fullStr |
Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments |
| title_full_unstemmed |
Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments |
| title_sort |
neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of t cell and dendritic cell compartments |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00207136_v131_n5_p1131_Soldati http://hdl.handle.net/20.500.12110/paper_00207136_v131_n5_p1131_Soldati |
| work_keys_str_mv |
AT salatinomariana neuroblastomatriggersanimmunoevasiveprograminvolvinggalectin1dependentmodulationoftcellanddendriticcellcompartments |
| _version_ |
1768542722629566464 |