T Cells from Multiple Myeloma Patients Exhibit Features of T-Cell Exhaustion

Immune evasion is a prerequisite for the establishment of cancers and has been delineated in several entities in detail. Recent studies suggest that immunological alterations involving the T-cell compartment are responsible for immune deficiencies. T cells progressively lose function and become exhausted. However, it remains largely unknown, whether and how T-cell exhaustion molecules play a role in multiple myeloma, a plasma cell tumor. Here, we investigated the phenotype and function of bone marrow T cells of multiple myeloma patients and healthy, age-matched donors. In the bone marrow of myeloma patients we found higher numbers of T cells expressing the molecules CTLA-4, CD160, CD244, PD1 and CD57, which are associated with T-cell exhaustion and T-cell senescence. Furthermore myeloma bone marrow T-cells showed a decreased proliferative capacity. Despite high CD107a expression of feshly isolated bone marrow T cells, CD8+ T cells did not retain the ability to degranulate in response to T-cell stimuli, as shown by an reduced transfer of CD107a to the cell surface upon stimulation. Additionally, while CD8+ T cells showed an increased expression of TBET, the ability to produce the cytokines IFNgamma, TNFalpha and IL-2 was reduced and could not be restored after T-cell activation. These data confirm the presence of hyperactivated but exhausted CD8+ T cells in multiple myeloma patients. Our results suggest that restoring the functional activity of bone marrow T-cells could enhance the efficacy of current immunotherapeutic strategies in multiple myeloma patients.