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Bone marrow-derived mesenchymal stem cells inhibit CD8 + T cell immune responses via PD-1/PD-L1 pathway in multiple myeloma.

Research paper by Zhaoyun Z Liu, Fu F Mi, Mei M Han, Mengyue M Tian, Ling L Deng, Nanhao N Meng, Jingyi J Luo, Rong R Fu

Indexed on: 19 Mar '21Published on: 19 Mar '21Published in: Clinical & Experimental Immunology



Abstract

High expression of the inhibitory receptor programmed death ligand 1 (PD-L1) on tumor cells and tumor stromal 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 signal pathway 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 newly diagnosed MM (NDMM) patients and the role of PD-1/PD-L1 pathway in BMSCs-mediated regulation of CD8 T cells. The data showed that the expression of PD-L1 on BMSCs in NDMM patients was significantly increased than that in normal controls(NC)(18.81±1.61% vs. 2.78±0.70 %; P<0.001). Furthermore, the PD-1 expression on CD8 T cells with NDMM patients was significantly higher than that in normal controls (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 suppressed CD8 T cells 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 in patients with MM may induce apoptosis of CD8 T cells through the PD-1/PD-L1 axis and inhibit the release of perforin and granzyme B from CD8 T cells so as to promote the immune escape of MM. This article is protected by copyright. All rights reserved.