Center for Cancer Immune Therapy, Department of Haematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Scand J Immunol. 2010 Dec;72(6):540-7. doi: 10.1111/j.1365-3083.2010.02463.x.
Patients with multiple myeloma (MM) suffer from a general impaired immunity comprising deficiencies in humoral responses, T-cell responses as well as dendritic cell (DC) function. Thus, to achieve control of tumour growth through immune therapy constitutes a challenge. Careful evaluation of the immune status in patients with MM seems crucial prior to active immune therapy. We evaluated the proportion of both, DC, Treg cells and myeloid-derived suppressor cells (MDSC) in peripheral blood from patients with MM at diagnosis and in remission as well as patients with monoclonal gammopathy of undetermined significance (MGUS). We found that the proportion of both myeloid (m) DC and plasmacytoid (p) DC in patients at diagnosis was lowered compared to control donors, while only the proportion of pDC in patients in remission and with MGUS was significantly lower than in controls. The proportion of CD4+FOXP3+ Treg cells was increased in patients at diagnosis and not in patients in remission or with MGUS. Also, Treg cells from patients with MM were functionally intact as they were able to inhibit proliferation of both CD4 and CD8 T cells. Finally, we observed an increase in the proportion of CD14+HLA-DR⁻/low MDSC in patients with MM at diagnosis, illustrating that this cell fraction is also distorted in patients with MM. Taken together, our results illustrate that, both mDC, pDC, Treg cells and MDSC are affected in patients with MM underlining the fact that the immune system is dysregulated as a consequence of the disease.
多发性骨髓瘤（MM）患者存在普遍的免疫功能受损，包括体液免疫应答、T 细胞应答以及树突状细胞（DC）功能缺陷。因此，通过免疫疗法控制肿瘤生长是一个挑战。在进行主动免疫治疗之前，仔细评估 MM 患者的免疫状态似乎至关重要。我们评估了诊断时和缓解期 MM 患者以及单克隆丙种球蛋白病不确定意义（MGUS）患者外周血中 DC、Treg 细胞和髓系来源抑制细胞（MDSC）的比例。我们发现，与对照供体相比，诊断时 MM 患者的髓样（m）DC 和浆细胞样（p）DC 的比例降低，而仅缓解期和 MGUS 患者的 pDC 比例明显低于对照。诊断时 CD4+FOXP3+Treg 细胞的比例增加，而缓解期或 MGUS 患者的比例没有增加。此外，MM 患者的 Treg 细胞功能完整，因为它们能够抑制 CD4 和 CD8 T 细胞的增殖。最后，我们观察到诊断时 MM 患者中 CD14+HLA-DR⁻/low MDSC 的比例增加，表明该细胞亚群在 MM 患者中也存在扭曲。总之，我们的结果表明，mDC、pDC、Treg 细胞和 MDSC 在 MM 患者中均受到影响，这突出了免疫系统因疾病而失调的事实。
