Enhanced expression of mir-181b in b cells of cll improves the anti-tumor cytotoxic t cell response

Mirco Di Marco, Serena Veschi, Paola Lanuti, Alice Ramassone, Stefania Pacillo, Sara Pagotto, Felice Pepe, Jonahunnatha Nesson George-William, Claudia Curcio, Marco Marchisio, Sebastiano Miscia, Idanna Innocenti, Francesco Autore, Barbara Vannata, Patrizia Di Gregorio, Mario Di Gioacchino, Silvia Valentinuzzi, Manuela Iezzi, Martina Iezzi, Renato Mariani-CostantiniLuigi Maria Larocca, Luca Laurenti, Angelo Veronese, Rosa Visone

Risultato della ricerca: Contributo in rivistaArticolo in rivista


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.
Lingua originaleEnglish
pagine (da-a)1-20
Numero di pagine20
Stato di pubblicazionePubblicato - 2021


  • CD40-CD40L
  • CLL
  • Cytotoxic T cells
  • MiR-181b
  • MicroRNA


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