肿瘤细胞治疗研究
英文原题：Pomalidomide enhances the maturation of dendritic cells derived from healthy donors and multiple myeloma patients.
pomalidomide 组与对照组 moDCs 分泌的 IL-12、TNF-α 和 MIP-1α 无显著差异（p = 0.458，p = 0.377，p = 0.248）。
目的：探讨泊马度胺对健康供者（HDs）和多发性骨髓瘤（MM）患者单核细胞衍生树突状细胞（moDCs）成熟的影响。方法：将外周血单个核细胞（PBMCs）中的单核细胞在含800 U/ml粒细胞-巨噬细胞集落刺激因子（GM-CSF）、500 U/ml白细胞介素-4（IL-4）、RPMI 1,640培养基、5%人血清、100 U/ml青霉素和0.1 mg/ml链霉素的培养基中孵育7天以生成moDCs。同时，孵育体系中加入10 µM泊马度胺或1 × PBS作为对照组。第8天收获细胞并通过流式细胞术分析。在FACS分析系统中，将总细胞中的CD80 + CD86 + 细胞群设门为moDCs。之后，分析moDCs上CD40和HLA-DR的表达。同时，通过酶联免疫吸附试验（ELISA）评估孵育体系上清液中细胞因子白细胞介素-12（IL-12）、肿瘤坏死因子-α（TNF-α）和巨噬细胞炎性蛋白1α（MIP-1α）的分泌。结果：当将所有HD-moDCs一起分析时（n = 15），与对照组相比，泊马度胺显著增加了moDCs上CD40表达和HLA-DR表达的平均荧光强度（MFI）（p = 0.003， p = 0.040）。同时，泊马度胺组中CD40 + moDCs和HLA-DR + moDCs占总moDCs的比例显著高于对照组（p = 0.008， p = 0.032）。当将所有MM患者-moDCs一起分析时（n = 11），与对照组相比，泊马度胺显著增加了moDCs上CD40表达和HLA-DR表达的MFI（p = 0.047， p = 0.006）。同时，pomalidomide 组中 HLA-DR + moDCs 占总 DCs 的比例显著高于对照组（p < 0.001）。此外，经 pomalidomide 处理的 HD-moDCs（n = 8）分泌的 IL-12、TNF-α 和 MIP-1α 分别为未处理 moDCs 的 192%、110% 和 112%（p = 0.020，p = 0.006，p = 0.055）。然而，当将 MM 患者-moDCs（n = 10）一起分析时，pomalidomide 组与对照组之间 moDCs 分泌的 IL-12、TNF-α 和 MIP-1α 无显著差异（p = 0.458，p = 0.377，p = 0.248）。结论：在体外，10 µM pomalidomide 可促进来源于 HDs 和 MM 患者的 moDCs 成熟。Pomalidomide 显示出作为 DC 佐剂应用于 MM 中基于 DC 的免疫治疗（如 DC 疫苗和 DC 细胞治疗）的潜力。
Objective: To explore the effect of pomalidomide on the maturation of monocyte-derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients. Methods: MoDCs were generated by the incubation of monocytes from peripheral blood mononuclear cells (PBMCs) for 7 days in a medium consisting of 800 U/ml granulocyte-macrophage colony stimulating factor (GM-CSF), 500 U/ml interleukin-4 (IL-4), RPMI 1,640 medium, 5% human serum, 100 U/ml penicillin and 0.1 mg/ml streptomycin. Meanwhile, the incubation system was administrated with 10 µM pomalidomide or 1 × PBS as the control group. On the eighth day, cells were harvested and analyzed by flow cytometry. The CD80 + CD86 + cell population in total cells was gated as moDCs in the FACS analyzing system. After that, the expression of CD40 and HLA-DR on moDCs was analyzed. Meanwhile, the supernatant from the incubation system was evaluated for the secretion of cytokines interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein 1α (MIP-1α) by enzyme-linked immunosorbent assay (ELISA). Results: When analyzing all the HD-moDCs together ( n = 15), pomalidomide significantly increased the mean fluorescence intensity (MFI) of CD40 expression and HLA-DR expression on moDCs compared with the control group ( p = 0.003, p = 0.040). Meanwhile, the proportion of CD40 + moDCs and HLA-DR + moDCs in total moDCs was significantly higher in the pomalidomide group than in the control group ( p = 0.008, p = 0.032). When analyzing all MM patient-moDCs together ( n = 11), pomalidomide significantly increased the MFI of CD40 expression and HLA-DR expression on moDCs compared with the control group ( p = 0.047, p = 0.006). Meanwhile, the proportion of HLA-DR + moDCs in total DCs was significantly higher in the pomalidomide group than in the control group ( p < 0.001). Moreover, HD-moDCs ( n = 8) treated with pomalidomide secreted 192% IL-12, 110% TNF-α, and 112% MIP-1α of the untreated moDCs ( p = 0.020, p = 0.006, p = 0.055). However, when analyzing MM patient-moDCs ( n = 10) together, the secretion of IL-12, TNF-α and MIP-1α from moDCs showed no significant difference between the pomalidomide group and the control group ( p = 0.458, p = 0.377, p = 0.248). Conclusion: In vitro , 10 µM pomalidomide enhances the maturation of moDCs derived from both HDs and MM patients. Pomalidomide shows potential to be applied as a DC adjuvant for DC-based immunotherapy, such as the DC vaccine and DC cell therapy in MM.
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