Enhanced Expression of miR-181b in B Cells of CLL Improves the Anti-Tumor Cytotoxic T Cell Response.

Autor: Di Marco M; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Veschi S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Lanuti P; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Ramassone A; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Pacillo S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Pagotto S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Pepe F; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., George-William JN; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Curcio C; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Marchisio M; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Miscia S; Department of Medicine and Aging Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Innocenti I; Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy., Autore F; Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy., Vannata B; Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy., Di Gregorio P; Institute of Transfusion Medicine, 'Ss. Annunziata' Hospital, 66100 Chieti, Italy., Di Gioacchino M; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Valentinuzzi S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Iezzi M; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Mariani-Costantini R; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Larocca LM; Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.; Institute of Transfusion Medicine, 'Ss. Annunziata' Hospital, 66100 Chieti, Italy.; Institute of Pathological Anatomy, Catholic University of Sacred Heart, 00168 Rome, Italy., Laurenti L; Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy., Veronese A; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy., Visone R; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, 66100 Chieti, Italy.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Jan 12; Vol. 13 (2). Date of Electronic Publication: 2021 Jan 12.
DOI: 10.3390/cancers13020257
Abstrakt: The clinical progression of B cell chronic lymphocytic leukemia (CLL) is associated with immune cell dysfunction and a strong decrease of miR-181b-5p ( miR-181b ), promoting the death of CLL cells. Here we investigated whether the reduction of miR-181b impairs the immune response in CLL. We demonstrate that activated CD4+ T cells increase miR-181b expression in CLL through CD40-CD40L signaling, which enhances the maturation and activity of cytotoxic T cells and, consequently, the apoptotic response of CLL cells. The cytotoxic response is facilitated by a depletion of the anti-inflammatory cytokine interleukin 10, targeted by miR-181b . In vivo experiments in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice confirmed that miR-181b promotes the apoptotic death of CLL cells only when functional T cells are restored. Overall, our findings suggest that the reinstatement of miR-181b in CLL cells could be an exploitable adjuvant therapeutic option for the treatment of CLL.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje