Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment
Articolo
Data di Pubblicazione:
2015
Citazione:
Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment / E. Assi, D. Cervia, L. Bizzozero, A. Capobianco, S. Pambianco, F. Morisi, C. De Palma, C. Moscheni, P. Pellegrino, E. Clementi, C. Perrotta. - In: MEDIATORS OF INFLAMMATION. - ISSN 0962-9351. - 2015:(2015), pp. 370482.1-370482.13. [10.1155/2015/370482]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
E. Assi, D. Cervia, L. Bizzozero, A. Capobianco, S. Pambianco, F. Morisi, C. De Palma, C. Moscheni, P. Pellegrino, E. Clementi, C. Perrotta
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