Koldehoff Michael, Lindemann Monika, Ross Stefan R, Elmaagacli Ahmet H
Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital of Essen, Essen, Germany.
Institute for Transfusion Medicine, University Hospital of Essen, Essen, Germany.
PLoS One. 2018 Jan 29;13(1):e0191482. doi: 10.1371/journal.pone.0191482. eCollection 2018.
Cytomegalovirus (HCMV) reactivation is found frequently after allogeneic hematopoietic stem cell transplantation (alloSCT) and is associated with an increased treatment-related mortality. Recent reports suggest a link between HCMV and a reduced risk of cancer progression in patients with acute leukemia or lymphoma after alloSCT. Here we show that HCMV can inhibit the proliferation of the acute myeloid leukemia cell line Kasumi-1 and the promyeloid leukemia cell line NB4. HCMV induced a significant up-regulation of HLA-class-II-molecules, especially HLA-DR expression and an increase of apoptosis, granzyme B, perforin and IFN-γ secretion in Kasumi-1 cells cocultured with peripheral blood mononuclear cells (PBMCs). Indolamin-2,3-dioxygenase on the other hand led only to a significant dose-dependent effect on IFN-γ secretion without effects on proliferation. The addition of CpG-rich oligonucleotides and ganciclovir reversed those antiproliferative effects. We conclude that HCMV can enhance alloreactivity of PBMCs against Kasumi-1 and NB4 cells in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required.
巨细胞病毒（HCMV）再激活在异基因造血干细胞移植（alloSCT）后很常见，并且与治疗相关死亡率增加有关。最近的报告表明，HCMV与alloSCT后急性白血病或淋巴瘤患者癌症进展风险降低之间存在联系。在这里，我们表明HCMV可以抑制急性髓系白血病细胞系Kasumi-1和早幼粒细胞白血病细胞系NB4的增殖。HCMV诱导与外周血单个核细胞（PBMC）共培养的Kasumi-1细胞中HLA-II类分子显著上调，尤其是HLA-DR表达，并增加细胞凋亡、颗粒酶B、穿孔素和IFN-γ分泌。另一方面，吲哚胺-2,3-双加氧酶仅对IFN-γ分泌产生显著的剂量依赖性影响，而对增殖无影响。添加富含CpG的寡核苷酸和更昔洛韦可逆转这些抗增殖作用。我们得出结论，HCMV可以在体外增强PBMC对Kasumi-1和NB4细胞的同种异体反应性。为了确定这种现象是否具有临床相关性，还需要进一步研究。
