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.

Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions.

The immunosuppressive properties of vascular endothelial growth factors (VEGFs) suggest a new role of angiogenic factors in T cell modulation in cancer and pregnancy. Most of VEGF effects on T cells are mediated through the VEGF receptor type 2 (VEGFR-2). This study aims to investigate the role of placental growth factor (PlGF) as a selective VEGFR-1 ligand in the modulation of human T cells functions.

Increased circulating CD3 T cells are associated with early relapse following autologous hematopoietic stem cell transplantation in patients with classical Hodgkin lymphoma.

Non-malignant host immune cells are the main substrate in classical Hodgkin lymphoma (HL) microenvironment. Reconstitution of lymphocyte populations following the high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) can support tumor growth in HL patients. We investigated recovery dynamics of circulating CD3, CD4, CD8, CD16/CD56, CD19, CD4FOXP3 lymphocytes following auto-HSCT in 79 HL patients and assessed relationship between these populations and the development of early relapse.

Increased circulating CD4FOXP3 T cells associate with early relapse following autologous hematopoietic stem cell transplantation in multiple myeloma patients.

Unlabelled: We investigated dynamics of CD4FOXP3 T cell recovery following the high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients. Circulating CD4FOXP3 T cells of 79 MM patients were evaluated using flow cytometry before HDC with auto-HSCT, at the day of engraftment, and following 6 and 12 months. Percentage of CD4FOXP3 T cells restored rapidly following auto-HSCT, became higher than pre-transplant level at the day of engraftment and then subsequently decreased for a year.

CD4 memory T cells retain surface expression of CD31 independently of thymic function in patients with lymphoproliferative disorders following autologous hematopoietic stem-cell transplantation.

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4CD45RACD31 T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4CD45RACD31 T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT.

Mesenchymal stromal cells improve early lymphocyte recovery and T cell reconstitution after autologous hematopoietic stem cell transplantation in patients with malignant lymphomas.

Mesenchymal stromal cells (MSCs) possess a multi-lineage potential and immunoregulatory activities and provide a great potential in cell-based technologies. However, MSC suppressive activity raises concerns regarding the possible adverse effect of MSCs on the immune recovery. The influence of autologous MSC co-transplantation on recovery of T cell subsets in patients receiving autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphomas and multiple myeloma were characterized.

[A case of chronic Budd-Chiari syndrome].

The Budd-Chiari syndrome is a rare disease associated with occlusion of the hepatic vein by a tumor or a thrombus. It develops due to progressive narrowing or occlusion of the hepatic veins and may occasionally proceed through the chronic disease within months, rarely years as individual recurrences, with pains, enlarged liver, and mild jaundice. These patients generally have partial hepatic vein occlusion.