Iranian Journal of Immunology

Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α

Document Type : Original Article

Authors

Yadan Wang 1
Xiaofei Wu 2
Yu Hu 1

1 Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

2 Institute of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

https://doi.org/10.22034/iji.2019.80279
Abstract
Background: Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. Objective: To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8+ T cells. Methods: Proliferation and cytotoxicity were detected by cell counting kit-8 assay. Cell cycle was detected by flow cytometry, and p16 expression was detected by PCR. The expression of fibroblast activation protein α (FAPα) was evaluated by immunohistochemistry. Results: Co-culture of CD8+ T cells with MM-BMSCs decreased the cell survival rate and increased the killing rate (p=0.03, p=0.001, respectively), the percentage of cells in G0/G1 phase and p16 expression (p<0.001). FAPα was mainly in the mesenchymal matrix of the MM microenvironment and elevated in MM derived bone marrow compared to healthy donors (p<0.001). The FAPα inhibitor PT-100, increased survival and the killing rate (p<0.001, p=0.043, respectively), and decreased the percentage of cells in G0/G1 phase and p16 expression (p=0.024, p=0.004, respectively). Conclusion: Therefore, MM-BMSCs inhibit the proliferation and cytotoxicity of CD8+ T cells, significantly block the cell cycle and increase p16 expression in co-cultured CD8+ T cells in a cell-cell contact-dependent manner.

Keywords

Bone Marrow Mesenchymal Stromal Cells
CD8+ T Cell Anergy
Fibroblast Activation Protein a
Multiple Myeloma
Iranian Journal of Immunology
Volume 16, Issue 4
Autumn 2019
Pages 278-290

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