Ni Ming, Wang Lei, Ding Yuntian, Gong Wenjie, Wang Sanmei, Neuber Brigitte, Schubert Maria-Luisa, Sauer Tim, Hückelhoven-Krauss Angela, Luft Thomas, Hegenbart Ute, Schönland Stefan, Eckstein Volker, Wang Jishi, Krüger William, Müller-Tidow Carsten, Dreger Peter, Schmitt Michael, Schmitt Anita
Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany; Department of Hematology, the Affiliated Hospital of Guizhou Medical University, Guizhou, China.
Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
Cytotherapy. 2022 Mar;24(3):311-319. doi: 10.1016/j.jcyt.2021.09.008. Epub 2021 Oct 25.
Extracorporeal photopheresis (ECP), a personalized cellular immunotherapy, constitutes a promising treatment for steroid-refractory/-resistant graft-versus-host disease (SR-GvHD), with encouraging clinical response rates. To further investigate its mechanism of action, ECP's effects on T helper (Th) cells as well as on expression of immune checkpoint (PD-1 and Tim-3) and apoptotic (Fas receptor [FasR]) molecules were investigated in 27 patients with SR-GvHD. Our data show that GvHD patients had significantly higher levels of Th2, Th17, Th22 and granulocyte-macrophage colony-stimulating factor (GM-CSF)-positive Th (ThG) cells and clearly lower levels of T follicular helper (Tfh) cells, including Th1- and Th2-like cells, compared with healthy donors. ECP therapy for GvHD was effective through the modulation of different Th subsets: increases of Th22 (1.52-fold) and Tfh cells (1.48-fold) in acute GvHD (aGvHD) and increases of Th2-like Tfh cells (1.74-fold) in chronic GvHD (cGvHD) patients were associated with clinical response. Expression of FasR was further upregulated in CD4CD8 T cells. Additionally, Tim-3-expressing effector T cells associated with the severity of GvHD were reduced. Taken together, these data show that ECP therapy exerts immunomodulatory effects by promoting a balanced immune reconstitution and inducing immune tolerance. Therefore it represents an attractive option for the treatment of GvHD.
体外光化学疗法（ECP）是一种个性化的细胞免疫疗法，是治疗类固醇难治性/抵抗性移植物抗宿主病（SR-GvHD）的一种有前景的治疗方法，临床缓解率令人鼓舞。为了进一步研究其作用机制，我们对27例SR-GvHD患者研究了ECP对辅助性T（Th）细胞以及免疫检查点（PD-1和Tim-3）和凋亡（Fas受体 [FasR]）分子表达的影响。我们的数据显示，与健康供者相比，GvHD患者的Th2、Th17、Th22和粒细胞-巨噬细胞集落刺激因子（GM-CSF）阳性Th（ThG）细胞水平显著更高，而包括Th1样和Th2样细胞在内的滤泡辅助性T（Tfh）细胞水平明显更低。GvHD的ECP治疗通过调节不同的Th亚群而有效：急性GvHD（aGvHD）中Th22细胞（1.52倍）和Tfh细胞（1.48倍）增加，慢性GvHD（cGvHD）患者中Th2样Tfh细胞（1.74倍）增加与临床缓解相关。FasR在CD4CD8 T细胞中的表达进一步上调。此外，与GvHD严重程度相关的表达Tim-3的效应T细胞减少。综上所述，这些数据表明ECP治疗通过促进平衡的免疫重建和诱导免疫耐受发挥免疫调节作用。因此，它是治疗GvHD的一个有吸引力的选择。
