Di Marco Mirco, Veschi Serena, Lanuti Paola, Ramassone Alice, Pacillo Stefania, Pagotto Sara, Pepe Felice, George-William Jonahunnatha Nesson, Curcio Claudia, Marchisio Marco, Miscia Sebastiano, Innocenti Idanna, Autore Francesco, Vannata Barbara, Di Gregorio Patrizia, Di Gioacchino Mario, Valentinuzzi Silvia, Iezzi Manuela, Mariani-Costantini Renato, Larocca Luigi Maria, Laurenti Luca, Veronese Angelo, Visone Rosa
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.
Cancers (Basel). 2021 Jan 12;13(2):257. doi: 10.3390/cancers13020257.
The clinical progression of B cell chronic lymphocytic leukemia (CLL) is associated with immune cell dysfunction and a strong decrease of (), promoting the death of CLL cells. Here we investigated whether the reduction of impairs the immune response in CLL. We demonstrate that activated CD4+ T cells increase 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 . In vivo experiments in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice confirmed that promotes the apoptotic death of CLL cells only when functional T cells are restored. Overall, our findings suggest that the reinstatement of in CLL cells could be an exploitable adjuvant therapeutic option for the treatment of CLL.
B细胞慢性淋巴细胞白血病（CLL）的临床进展与免疫细胞功能障碍以及（）的显著降低有关，从而促进CLL细胞的死亡。在此，我们研究了（）的减少是否会损害CLL中的免疫反应。我们证明，活化的CD4+T细胞通过CD40-CD40L信号通路增加CLL中（）的表达，这增强了细胞毒性T细胞的成熟和活性，进而增强了CLL细胞的凋亡反应。抗炎细胞因子白细胞介素10的消耗促进了细胞毒性反应，（）靶向该细胞因子。在NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ小鼠中进行的体内实验证实，只有当功能性T细胞恢复时，（）才会促进CLL细胞的凋亡死亡。总体而言，我们的研究结果表明，恢复CLL细胞中的（）可能是一种可利用的辅助治疗选择，用于治疗CLL。
