AUTHOR=Wang Xi , Dai Jingying , Xia Jingyi , Ye Zichen , Huang Xiaobing , Cao Wanjun , Xiao Rong , He Lin 

TITLE=Pomalidomide enhances the maturation of dendritic cells derived from healthy donors and multiple myeloma patients

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1076096

DOI=10.3389/fphar.2022.1076096

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To explore the effect of pomalidomide on the maturation of monocyte-derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients.</p><p><bold>Methods:</bold> 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<sup>+</sup>CD86<sup>+</sup> 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).</p><p><bold>Results:</bold> When analyzing all the HD-moDCs together (<italic>n</italic> = 15), pomalidomide significantly increased the mean fluorescence intensity (MFI) of CD40 expression and HLA-DR expression on moDCs compared with the control group (<italic>p</italic> = 0.003, <italic>p</italic> = 0.040). Meanwhile, the proportion of CD40<sup>+</sup> moDCs and HLA-DR<sup>+</sup> moDCs in total moDCs was significantly higher in the pomalidomide group than in the control group (<italic>p</italic> = 0.008, <italic>p</italic> = 0.032). When analyzing all MM patient-moDCs together (<italic>n</italic> = 11), pomalidomide significantly increased the MFI of CD40 expression and HLA-DR expression on moDCs compared with the control group (<italic>p</italic> = 0.047, <italic>p</italic> = 0.006). Meanwhile, the proportion of HLA-DR<sup>+</sup> moDCs in total DCs was significantly higher in the pomalidomide group than in the control group (<italic>p</italic> &lt; 0.001). Moreover, HD-moDCs (<italic>n</italic> = 8) treated with pomalidomide secreted 192% IL-12, 110% TNF-α, and 112% MIP-1α of the untreated moDCs (<italic>p</italic> = 0.020, <italic>p</italic> = 0.006, <italic>p</italic> = 0.055). However, when analyzing MM patient-moDCs (<italic>n</italic> = 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 (<italic>p</italic> = 0.458, <italic>p</italic> = 0.377, <italic>p</italic> = 0.248).</p><p><bold>Conclusion:</bold><italic>In vitro</italic>, 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.</p>