BM-derived Tregs and myeloma-specific immunity during SCM
Takahashi S, Minnie SA, Ensbey KS, et al. Regulatory T Cells Suppress Myeloma-Specific Immunity During Autologous Stem Cell Mobilization and Transplantation. Blood. 2024; (doi: 10.1182/blood.2023022000).
Highly immunosuppressive regulatory T cells (Treg) contribute to inadequate responses and eventual disease progression in myeloma patients after autologous stem cell transplantation (ASCT), according to researchers, who say Treg depletion can improve this prognosis. Their study established that Treg is highly expressed in patient mobilized stem cell grafts, which at the same time are populated by large volumes of effector CD8 T cells. Using a preclinical myeloma model to observe Treg-associated activity during stem cell mobilization (SCM), the researchers found that aggressive Treg deletion during this process produced SCM grafts with polyfunctional CD8 T effector memory cells that significantly increased anti-myeloma immunity after ASCT. Further investigation determined that Treg depletion could not be achieved through antibody-based approaches; however, a synthetic IL-2/IL-15 mimetic successfully replicated the scenario. The mimetic stimulates the IL-2 receptor on CD8 T cells without binding to the high-affinity IL-2Ra preferred by Treg, thus expanding effector cells in mobilized grafts and preventing disease progression.