Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells.

Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells.

Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells / Zitti, B°; Molfetta, R°; Fionda, C; Quatrini, L; Stabile, H; Lecce, M; De Turris, V; Ricciardi, Mr; Petrucci, Mt; Cippitelli, M; Gismondi, A; Santoni, A; Paolini, R; °these Authors Contributed Equally To The, Work. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 7:1(2017), p. 10445. [10.1038/s41598-017-10403-0]

Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells

Zitti B°;Molfetta R°
;
Fionda C;Quatrini L;Stabile H;Lecce M;Ricciardi Mr;Petrucci Mt;Cippitelli M;Gismondi A;Santoni A;Paolini R
;
2017

Abstract

Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells.
2017
Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells.
Sumoylation; NK; PVR
01 Pubblicazione su rivista::01a Articolo in rivista
Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells / Zitti, B°; Molfetta, R°; Fionda, C; Quatrini, L; Stabile, H; Lecce, M; De Turris, V; Ricciardi, Mr; Petrucci, Mt; Cippitelli, M; Gismondi, A; Santoni, A; Paolini, R; °these Authors Contributed Equally To The, Work. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 7:1(2017), p. 10445. [10.1038/s41598-017-10403-0]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1003837
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