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Bone marrow -derived mesenchymal stem cells inhibiting CD8+ T cell immune responses via PD-1/PD-L1 pathway in multiple myeloma
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  • zhaoyun liu,
  • Fu Mi,
  • Mei Han,
  • Mengyue Tian,
  • Ling Deng,
  • Nanhao Meng,
  • Jingyi Luo,
  • Rong Fu
zhaoyun liu
Tianjin Medical University General Hospital
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Fu Mi
Tianjin Medical University General Hospital
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Mei Han
Tianjin Medical University General Hospital
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Mengyue Tian
Tianjin Medical University General Hospital
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Ling Deng
Tianjin Medical University General Hospital
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Nanhao Meng
Tianjin Medical University General Hospital
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Jingyi Luo
Tianjin Medical University General Hospital
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Rong Fu
Tianjin medical university general hospital
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Abstract

High expression of the inhibitory receptor programmed death ligand 1 (PD-L1) on the surface of tumor cells have been found play a key role in tumor immune evasion in several human malignancies. However, the expression of PD-L1 on bone marrow mesenchymal stem cells (BMSCs) and whether the PD-1/PD-L1 axis is involved in the BMSCs versus T cell immune response in Multiple Myeloma (MM) remain poorly defined. In this study, we explored the expression of PD-L1 on BMSCs from MM patients and the role of PD-1/PD-L1 pathway in BMSCs-mediated regulation of CD8+T cells. We observed that the expression of PD-L1 on BMSCs was significantly higher in NDMM group, compared with the NC group (18.81±1.61% vs. 2.78±0.70 %; P<0.001). Furthermore, the expression of PD-1 on CD8+ T cells in NDMM group was significantly higher than that in control group (43.22±2.98% vs. 20.71±1.08%; P<0.001). However, there was no significant difference in PD-1 expression of CD4+ T cells and NK cells between NDMM group and NC group. Additionally, the co-culture assays revealed that BMSCs significantly promoted CD8+ T cell apoptosis and suppressed CD8+ T cell function. However, PD-L1 inhibitor effectively reversed BMSCs-mediated suppression in CD8+ T cells. We also found that the combination of PD-L1 inhibitor and pomalidomide can further enhance the killing effect of CD8+ T cells on MM cells. In summary, our findings demonstrated that BMSCs may induce apoptosis and functional imbalance of CD8+ T cells via PD-1/PD-L1 pathway and promote the immunity escape of MM.