Экспрессия ингибиторных сигнальных молекул PD-1 и TIM-3 Т-лимфоцитами в раннем посттрансплантационном периоде у больных множественной миеломой

Introduction . High-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of treatment for multiple myeloma (MM) patients. The post-transplant period appears to be promising for targeted anti-checkpoint therapy in MM. Aim — to study the dynamics and functional properties of T-cells expressing inhibitory checkpoint molecules PD-1 and TIM-3 in patients with MM under conditions of lymphopenia after HDC with auto-HSCT. Methods . The study included 40 patients with MM who underwent HDC with auto-HSCT. The counts of PD-1- and TIM3-positive CD8 + and CD4 + T-cells and their functional activity on the intracellular expression of Ki-67, production of granzyme B, and interferon-γ were assessed by fl ow cytometry. Results . Relative counts of patient PD-1 + and TIM-3 + subsets of CD8 + and CD4 + T-cells obtained from bone marrow samples were higher compared to peripheral blood. CD8 + PD-1 + and CD4 + PD-1 + T-cells of MM patients had a pronounced cytotoxic and cytokine-producing potential. The functional activity of CD8 + TIM-3 + and CD4 + TIM-3 + T-cells was signifi cantly reduced compared with TIM-3-negative subsets. Low functional activity was also detected in populations of CD8 + and CD4 + T-lympho cytes, co-expressing PD-1 and TIM-3. The frequencies of T-cells expressing PD-1 and TIM-3 increased signifi cantly on the engraftment day after auto-HSCT. The proliferative activity of PD-1 + and TIM-3 + CD4 + and CD8 + T-cells and the cytotoxic potential of PD-1 + and TIM-3 + CD8 + T-cells were also signifi cantly increased compared to the data prior auto-HSCT. Conclusions . PD-1-positive T-cells in MM patients are related to activated or “early dysfunctional” but not exhausted subsets, while T-cells exhaustion is more analogous with CD8 + TIM-3 + and CD4 + TIM-3 + T-cells, as well as with subsets co-expressing PD-1 and TIM-3. To identify the state of T-cells exhaustion, it is necessary to evaluate T-cells subsets co-expressing PD-1, TIM-3, and other ICMs, and/or to study their functional properties. In the early post-transplant period, the proportion of Tcells expressing PD-1 and TIM-3 increases due to an increase in their proliferative potential.