PD-1 and TIM-3 T cells widely express common γ-chain cytokine receptors in multiple myeloma patients, and IL-2, IL-7, IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells.

Background: Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma (MM) progression. Simultaneously, previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with common γ-chain family cytokines and during homeostatic proliferation. The aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets up-regulating PD-1 and TIM-3 checkpoint molecules.

Decreased circulating myeloid-derived suppressor cell count at the engraftment is one of the risk factors for multiple myeloma relapse after autologous hematopoietic stem cell transplantation.

Recent studies demonstrated that myeloid-derived suppressor cells (MDSCs) are involved in the pathogenesis and progression of multiple myeloma (MM). Nevertheless, data on the quantitative and functional changes in MDSCs during standard MM treatment remain poorly understood. Here, we determined that monocytic MDSCs (M-MDSC; CD14HLA-DR) and granulocytic MDSCs (PMN-MDSC; LinHLA-DRCD33CD66b) in MM patients in remission following induction therapy (IT) were significantly increased, while early MDSCs (E-MDSCs; LinHLA-DRCD33CD66b) were decreased compared to the donor group.

Expression of Inhibitory Molecules (Arginase-1, IDO, and PD-L1) by Myeloid-Derived Suppressor Cells in Multiple Myeloma Patients in Remission.

We studied suppressor potential of myeloid-derived suppressor cells (MDSC) in multiple myeloma patients, including before and after mobilization of hematopoietic stem cells (HSC), by evaluating the expression of arginase-1 (Arg1), indolamine-2,3-dioxygenase (IDO), and PD-L1 in MDSC subsets. The study included 20 multiple myeloma patients in remission, 5 patients with progression, as well as 10 sex-and age-matched healthy donors. The expression of Arg1, IDO, and PD-L1 in circulating granulocytic MDSC (G-MDSC, LinHLA-DRCD33CD66b), monocytic MDSC (M-MDSC, CD14HLA-DR), and early-stage MDSC (E-MDSC, LinHLA-DRCD33CD66b) was evaluated by flow cytometry.

Highly proliferative and functional PD-1 and TIM-3 T cells are transiently increased in multiple myeloma following autologous hematopoietic stem cell transplantation.

The aim of our prospective study was to assess recovery dynamics and functional characteristics of PD-1 and TIM-3 T cells in multiple myeloma (MM) patients following high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (AHSCT). Peripheral blood, autograft and bone marrow samples were obtained from 46 MM patients before conditioning, at the engraftment, following six and 12 months post-transplant. Frequencies of CD4 and CD8 T cells expressing PD-1 and TIM-3 and intracellular expression of Ki-67 and Granzyme B were evaluated.

Quantitative and functional characteristics of circulating and bone marrow PD-1- and TIM-3-positive T cells in treated multiple myeloma patients.

The aim of the present work was to evaluate counts and functional properties of PD-1 and TIM-3 T cells in peripheral blood (PB) and bone marrow (BM) of multiple myeloma (MM) patients following the induction therapy. Sixty patients were enrolled in the study, CD4 and CD8 T cells expressing PD-1 and TIM-3, intracellular production of IFNγ and intracellular expression of Granzyme B were assessed. Relative counts of the majority of circulating PD-1, TIM-3 and PD-1TIM-3 T cells were higher in MM patients with disease progression compared with individuals in remission.