Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment. (26th May 2015)

• Record Type: Journal Article
• Authors: Assi, Emma; Cervia, Davide; Bizzozero, Laura; Capobianco, Annalisa; Pambianco, Sarah; Morisi, Federica; De Palma, Clara; Moscheni, Claudia; Pellegrino, Paolo; Clementi, Emilio; Perrotta, Cristiana
• Other Names: Agrawal Anshu Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2015(2015)
• Publication Date: 2015-05-26
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2015/370482
• Languages: English
• ISSNs: 0962-9351

Abstract

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.