Instituto de Biomedicina de Sevilla (IBiS/CSIC/Universidad de Sevilla), Seville, Spain.
Centro de Investigación Biomédica en Red en Cáncer-CIBERONC, Madrid, Spain.
Sci Rep. 2022 May 19;12(1):8348. doi: 10.1038/s41598-022-12407-x.
Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if the combined use of both agents can exert a synergistic effect in the treatment of GvHD. For this purpose, we studied the effect of this combination both in vitro and in a GvHD mouse model. Our results show that ruxolitinib favors the ratio of thymic regulatory T cells to conventional T cells in culture, without affecting the suppressive capacity of these Treg. The combination of ruxolitinib with Treg showed a higher efficacy as compared to each single treatment alone in our GvHD mouse model in terms of GvHD incidence, severity and survival without hampering graft versus leukemia effect. This beneficial effect correlated with the detection in the bone marrow of recipient mice of the infused donor allogeneic Treg after the adoptive transfer.
供体来源的调节性 T 淋巴细胞和 JAK1/2 激酶抑制剂芦可替尼目前正在被评估作为治疗慢性移植物抗宿主病（cGvHD）的治疗选择。在这项工作中，我们旨在确定这两种药物的联合使用是否能在 GvHD 的治疗中发挥协同作用。为此，我们研究了这一组合在体外和 GvHD 小鼠模型中的作用。我们的结果表明，芦可替尼在培养物中有利于胸腺调节性 T 细胞与常规 T 细胞的比率，而不影响这些 Treg 的抑制能力。与每种单一治疗相比，在我们的 GvHD 小鼠模型中，芦可替尼与 Treg 的组合在 GvHD 的发生率、严重程度和存活率方面表现出更高的疗效，而不会损害移植物抗白血病效应。这种有益的效果与在接受过继转移的受体小鼠的骨髓中检测到输注的供体同种异体 Treg 相关。
