Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment
The inflammatory microenvironment induces tumours to acquire an aggressive and immunosuppressive behaviour. Since acid sphingomyelinase (A-SMase) downregulation in melanoma was shown to determine a malignant phenotype, we aimed here to elucidate the role of A-SMase in the regulation of tumour immuno...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/370482 |
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| author | Emma Assi Davide Cervia Laura Bizzozero Annalisa Capobianco Sarah Pambianco Federica Morisi Clara De Palma Claudia Moscheni Paolo Pellegrino Emilio Clementi Cristiana Perrotta |
| author_facet | Emma Assi Davide Cervia Laura Bizzozero Annalisa Capobianco Sarah Pambianco Federica Morisi Clara De Palma Claudia Moscheni Paolo Pellegrino Emilio Clementi Cristiana Perrotta |
| author_sort | Emma Assi |
| collection | DOAJ |
| description | The inflammatory microenvironment induces tumours to acquire an aggressive and immunosuppressive behaviour. Since acid sphingomyelinase (A-SMase) downregulation in melanoma was shown to determine a malignant phenotype, we aimed here to elucidate the role of A-SMase in the regulation of tumour immunogenic microenvironment using in vivo melanoma models in which A-SMase was either downregulated or maintained at constitutively high levels. We found high levels of inflammatory factors in low A-SMase expressing tumours, which also displayed an immunosuppressive/protumoural microenvironment: high levels of myeloid-derived suppressor cells (MDSCs) and regulatory T lymphocytes (Tregs), as well as low levels of dendritic cells (DCs). In contrast, the restoration of A-SMase in melanoma cells not only reduced tumour growth and immunosuppression, but also induced a high recruitment at tumour site of effector immune cells with an antitumoural function. Indeed, we observed a poor homing of MDSCs and Tregs and the increased recruitment of CD8+ and CD4+ T lymphocytes as well as the infiltration of DCs and CD8+/CD44high T lymphocytes. This study demonstrates that change of A-SMase expression in cancer cells is sufficient per se to tune in vivo melanoma growth and that A-SMase levels modulate immune cells at tumour site. This may be taken into consideration in the setting of therapeutic strategies. |
| format | Article |
| id | doaj-art-b30b3bbe561a4f39882c46a9a0863004 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b30b3bbe561a4f39882c46a9a08630042025-02-03T05:57:40ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/370482370482Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune MicroenvironmentEmma Assi0Davide Cervia1Laura Bizzozero2Annalisa Capobianco3Sarah Pambianco4Federica Morisi5Clara De Palma6Claudia Moscheni7Paolo Pellegrino8Emilio Clementi9Cristiana Perrotta10Scientific Institute IRCCS Eugenio Medea, 23842 Bosisio Parini, ItalyUnit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, ItalyScientific Institute IRCCS Eugenio Medea, 23842 Bosisio Parini, ItalyDivision of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milan, ItalyUnit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, ItalyUnit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, ItalyUnit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, ItalyUnit of Morphology, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), Università di Milano, 20157 Milan, ItalyUnit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, ItalyScientific Institute IRCCS Eugenio Medea, 23842 Bosisio Parini, ItalyUnit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, ItalyThe inflammatory microenvironment induces tumours to acquire an aggressive and immunosuppressive behaviour. Since acid sphingomyelinase (A-SMase) downregulation in melanoma was shown to determine a malignant phenotype, we aimed here to elucidate the role of A-SMase in the regulation of tumour immunogenic microenvironment using in vivo melanoma models in which A-SMase was either downregulated or maintained at constitutively high levels. We found high levels of inflammatory factors in low A-SMase expressing tumours, which also displayed an immunosuppressive/protumoural microenvironment: high levels of myeloid-derived suppressor cells (MDSCs) and regulatory T lymphocytes (Tregs), as well as low levels of dendritic cells (DCs). In contrast, the restoration of A-SMase in melanoma cells not only reduced tumour growth and immunosuppression, but also induced a high recruitment at tumour site of effector immune cells with an antitumoural function. Indeed, we observed a poor homing of MDSCs and Tregs and the increased recruitment of CD8+ and CD4+ T lymphocytes as well as the infiltration of DCs and CD8+/CD44high T lymphocytes. This study demonstrates that change of A-SMase expression in cancer cells is sufficient per se to tune in vivo melanoma growth and that A-SMase levels modulate immune cells at tumour site. This may be taken into consideration in the setting of therapeutic strategies.http://dx.doi.org/10.1155/2015/370482 |
| spellingShingle | Emma Assi Davide Cervia Laura Bizzozero Annalisa Capobianco Sarah Pambianco Federica Morisi Clara De Palma Claudia Moscheni Paolo Pellegrino Emilio Clementi Cristiana Perrotta Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment Mediators of Inflammation |
| title | Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment |
| title_full | Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment |
| title_fullStr | Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment |
| title_full_unstemmed | Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment |
| title_short | Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment |
| title_sort | modulation of acid sphingomyelinase in melanoma reprogrammes the tumour immune microenvironment |
| url | http://dx.doi.org/10.1155/2015/370482 |
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