TY - JOUR
T1 - Enhanced expression of mir-181b in b cells of cll improves the anti-tumor cytotoxic t cell response
AU - Di Marco, Mirco
AU - Veschi, Serena
AU - Lanuti, Paola
AU - Ramassone, Alice
AU - Pacillo, Stefania
AU - Pagotto, Sara
AU - Pepe, Felice
AU - George-William, Jonahunnatha Nesson
AU - Curcio, Claudia
AU - Marchisio, Marco
AU - Miscia, Sebastiano
AU - Innocenti, Idanna
AU - Autore, Francesco
AU - Vannata, Barbara
AU - Di Gregorio, Patrizia
AU - Di Gioacchino, Mario
AU - Valentinuzzi, Silvia
AU - Iezzi, Manuela
AU - Iezzi, Martina
AU - Mariani-Costantini, Renato
AU - Larocca, Luigi Maria
AU - Laurenti, Luca
AU - Veronese, Angelo
AU - Visone, Rosa
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - CD40-CD40L
KW - CLL
KW - Cytotoxic T cells
KW - MiR-181b
KW - MicroRNA
KW - CD40-CD40L
KW - CLL
KW - Cytotoxic T cells
KW - MiR-181b
KW - MicroRNA
UR - http://hdl.handle.net/10807/184584
U2 - 10.3390/cancers13020257
DO - 10.3390/cancers13020257
M3 - Article
SN - 2072-6694
VL - 13
SP - 1
EP - 20
JO - Cancers
JF - Cancers
ER -