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Background    Prognosis of multiple myeloma (MM) patients with extramedullary disease (EMD) remains poor. T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow (BM) of MM patients. However, the immunosuppressive microenvironment and immune checkpoint receptors (ICRs) on CD8 +  T cells in the EMD tissue of newly diagnosed MM (NDMM) patients have not been thoroughly studied.Methods    We investigated the expression levels of T cell immunoglobulin mucin-domain-containing-3 (TIM-3) and T-cell immunoglobulin and ITIM domain (TIGIT) on CD8 +  T cells and the expression of their ligands (Galectin-9 and CD155) on myeloma cells in EMD tissue of NDMM patients. The expression levels of TIM-3 and TIGIT on T cells and their ligands (Galectin-9 and CD155) on myeloma cells were analyzed by multicolored fluorescent flow cytometry in the peripheral blood (PB), BM, and EMD tissue. Additionally, the expression of ICRs was compared among PB, BM, and EMD tissue.Results    The expression levels of TIGIT and TIM-3 on CD8 +  T cell subsets, including CD8 +  Naïve T (T N ) cells and CD8 +  terminally differentiated effector memory T (T EMRA ) cells, were significantly higher in EMD than in PB ( p  &lt; 0.05 for all). The expression levels of TIGIT and TIM-3 on CD8 +  T N  cells were higher in EMD than in BM ( p  &lt; 0.05 for all). There were no differences in Galectin-9 and CD155 expression on myeloma cells among PB, BM, and EMD tissue.Conclusion    Our data add new evidence that T cells express increased TIGIT and TIM-3, suggesting that there may be T-cell exhaustion in EMD of patients with MM.

Immune checkpoint receptors and their ligands on CD8 + T cells and myeloma cells in extramedullary multiple myeloma