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

Abstract

<strong>Background:</strong> Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. <strong>Objective:</strong> To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8⁺ T cells. <strong>Methods:</strong> 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. <strong>Results:</strong> 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). <strong>Conclusion:</strong> 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.