Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460251/ https://www.ncbi.nlm.nih.gov/pubmed/26101462 http://dx.doi.org/10.1155/2015/370482 |
_version_ | 1782375356634759168 |
---|---|
author | Assi, Emma Cervia, Davide Bizzozero, Laura Capobianco, Annalisa Pambianco, Sarah Morisi, Federica De Palma, Clara Moscheni, Claudia Pellegrino, Paolo Clementi, Emilio Perrotta, Cristiana |
author_facet | Assi, Emma Cervia, Davide Bizzozero, Laura Capobianco, Annalisa Pambianco, Sarah Morisi, Federica De Palma, Clara Moscheni, Claudia Pellegrino, Paolo Clementi, Emilio Perrotta, Cristiana |
author_sort | Assi, Emma |
collection | PubMed |
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(+)/CD44(high) 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 | Online Article Text |
id | pubmed-4460251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-44602512015-06-22 Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment Assi, Emma Cervia, Davide Bizzozero, Laura Capobianco, Annalisa Pambianco, Sarah Morisi, Federica De Palma, Clara Moscheni, Claudia Pellegrino, Paolo Clementi, Emilio Perrotta, Cristiana Mediators Inflamm Research Article 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(+)/CD44(high) 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. Hindawi Publishing Corporation 2015 2015-05-26 /pmc/articles/PMC4460251/ /pubmed/26101462 http://dx.doi.org/10.1155/2015/370482 Text en Copyright © 2015 Emma Assi et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Assi, Emma Cervia, Davide Bizzozero, Laura Capobianco, Annalisa Pambianco, Sarah Morisi, Federica De Palma, Clara Moscheni, Claudia Pellegrino, Paolo Clementi, Emilio Perrotta, Cristiana Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460251/ https://www.ncbi.nlm.nih.gov/pubmed/26101462 http://dx.doi.org/10.1155/2015/370482 |
work_keys_str_mv | AT assiemma modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT cerviadavide modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT bizzozerolaura modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT capobiancoannalisa modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT pambiancosarah modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT morisifederica modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT depalmaclara modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT moscheniclaudia modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT pellegrinopaolo modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT clementiemilio modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment AT perrottacristiana modulationofacidsphingomyelinaseinmelanomareprogrammesthetumourimmunemicroenvironment |