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Newly Found Peacekeeper: Potential of CD8+ Tregs for Graft-Versus-Host Disease.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most effective and potentially curative treatment for a variety of hematologic malignancies. However, graft-versus-host disease (GVHD) is a major obstacle that limits wide application of allo-HSCT, despite the development of prophylactic strategies. Owing to experimental and clinical advances in the field, GVHD is characterized by disruption of the balance between effector and regulatory immune cells, resulting in higher inflammatory cytokine levels. A reduction in regulatory T cells (Tregs) has been associated with lim

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… Human CD8+CD25+ Thymocytes Share Phenotypic and Functional Features With CD4+CD25+ Regulatory Thymocytes. Blood (2003) 102:4107–14. doi: 10.1182/blood-2003-04-1320 50. Zheng SG, Wang JH, Koss MN, Quismorio FJ, Gray JD, Horwitz DA. …

Allogeneic Hematopoietic Transplantation for Multiple Myeloma in the New Drugs Era: A Platform to Cure.

Allogeneic hematopoietic cell transplantation (alloHCT) represents a treatment option for multiple myeloma (MM) patients. As shown in several studies, alloHCT is highly effective, but it is hampered by a high toxicity, mainly related to the graft-versus-host disease (GVHD), a complex immunological reaction ascribable to the donor's immune system. The morbidity and mortality associated with GVHD can weaken the benefits of this procedure. On the other side, the high therapeutic potential of alloHCT is also related to the donor's immune system, through immunological activity known as the graft-ve

Study protocol: Close Assessment and Testing for Chronic Graft-vs.-Host disease (CATCH).

Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The "Close Assessment and Testing for Chronic GVHD (CATCH)" study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through

Patients Undergoing Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation Exhibit Depleted Vitamin C Status in Association with Febrile Neutropenia.

Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing conditioning chemotherapy and HSCT. Blood samples were collected prior to transplantation, at one week, two weeks and four weeks following transplantation. Vitamin C status and biomarkers of inflammation (C-reactive protein) and oxidative stress (protein car

Совершенствование иммунотерапии клеток ИНКТ путем интеграции оптимизированных эндодоменов ЦАР и участников ИНКТ.

Клетки ИНКТ становятся весьма перспективной платформой иммунотерапии для лечения рака. Чтобы максимально увеличить антираковую активность CAR-INKT против рака крови, мы изучили оптимальные конструкции CAR и их комбинацию с новыми специфичными участниками INKT. Мы находим, что среди пяти различных эндодомен ЦАР, подкрепляемых возросшей вспыльчивостью и перекрестным разговором между Plexin D1 на CAR-INKT и Semaphorin 4 A на клетках миэломы, BCMA CD28z CAR-INKT проявляет наибольшую активность против миэломы. В частности, CD28z CAR-INKT опережает их коллег CAR-T. В целях расширения потенциала CAR-

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… Plxnd1, through its interaction with Sema3E, is required for migration of positively selected thymocytes into the medulla of the thymus 39 , while interaction of the Plxnd1-associated receptor Neuropilin 1 with Sema4A promotes transcriptional and functional stability of Tregs 40 . … PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla. Immunity 29 , 888–898 (2008). 40. Delgoffe, G. M. et al. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature 501 , 252–256 (2013). 41. Naito, Y. et al. …

Prospects for γδ T cells and chimeric antigen receptor γδ T cells in cancer immunotherapy.

γδ T cells, a type of specialized T cell, differ from alpha-beta T cells due to the presence of γ and δ chain surface T cell receptors. These receptors allow them to directly recognize and bind antigenic molecules without the requirement of attachment to MHC or APC antigen presentation. Given their intrinsic properties and functional versatility, γδ T cells are under intensive investigation as carriers for chimeric antigen receptor (CAR) in the context of cancer therapy. In this regard, γδ CAR-T cells have demonstrated great potential to overcome the limitations of antigen recognition with the

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… Attenuation of gammadeltatcr signaling efficiently diverts thymocytes to the alphabeta lineage. Immunity. (2005) 22:595–606. doi: 10.1016/j.immuni.2005.04.003 24. Chien YH, Meyer C, Bonneville M. Γδ T cells: first line of defense and beyond. … T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. J Immunol (Baltimore Md: 1950). (1989) 142:2112–21. doi: 10.4049/jimmunol.142.6.2112 32. Bonneville M, O’Brien RL, Born WK. …

Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications.

Background: Since the 1990s, transplantations of hematopoietic and mesenchymal stem cells (HSCT and MSCT) and dendritic cell (DCT) have been investigated for the treatment of neurological autoimmune disorders (NADs). With the growing number of transplanted patients, awareness of neuroimmunolgical complications has increased. Therefore, an overview of SCT for the most common NADs and reports of secondary immunity after SCT is provided. Methods: For this narrative review, a literature search of the PubMed database was performed. A total of 86 articles reporting on different SCTs in NADs and 61 a

Development and Applications of Prognostic Risk Models in the Management of Invasive Mold Disease.

Prognostic models or risk scores are frequently used to aid individualize risk assessment for diseases with multiple, complex risk factors and diagnostic challenges. However, relatively little attention has been paid to the development of risk models for invasive mold diseases encountered in patients with hematological malignancies, despite a large body of epidemiological research. Herein we review recent studies that have described the development of prognostic models for mold disease, summarize our experience with the development and clinical use of one such model (BOSCORE), and discuss the

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is

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… Hossain et al demonstrated the disruption of β-catenin and TCF interaction hinders T-cell survival due to increased susceptibility of thymocytes and activated T-cells to apoptosis. It has been reported that canonical and non-canonical Wnt ligands have differing effects on B-cell development. … ICAT expression resulted in increased susceptibility of thymocytes and activated T-cells to apoptosis. …

IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.

Chronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21-62 years) that received at least two prior lines of therapy for

Impact of pretransplant donor and recipient cytomegalovirus serostatus on outcome for multiple myeloma patients undergoing reduced intensity conditioning allogeneic stem cell transplantation.

Scope of the study was to investigate the impact of pre-transplant CMV serostatus of the donor and/or recipient on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer center at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R] -) 1

Cytokines in tear fluid of patients with ocular graft-versus-host disease after allogeneic stem cell transplantation.

PurposeTo investigate the profile of cytokines in tear fluid of patients after allogeneic stem cell transplantation (allo-SCT) and determine their relation to the presence and manifestations of ocular graft-versus-host disease (GvHD).MethodsIn this cross sectional study tear fluid was collected in 34 consecutive adult patients that previously underwent allo-SCT (16 with ocular GvHD and 18 without) and 16 age- and gender-matched healthy controls using the Schirmer test under local anesthesia. Tear fluid was analyzed by multiplex immunoassay for the presence of interleukin (IL)-2, IL-4, IL-6, IL

Consistent FFP2-masking as part of reducing viral respiratory infections on medical wards for allogeneic hematopoietic stem cell transplantation.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year. Each group consisted of 150 matched patients. The usage of FFP2 masks reduced the incidence

Efficacy and Safety of a DOAC Compared to Unfractionated Heparin and A Low Molecular Weight Heparin in the Prevention of Thromboembolism in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) patients are at risk of thromboembolic events, making thromboprophylaxis crucial. OBJECTIVES: This study aimed to compare apixaban, a direct factor Xa inhibitor (DOAC), with dalteparin and unfractionated heparin for thromboprophylaxis in HSCT recipients. The safety outcome included the assessment of hemorrhagic events. METHODS: In this open-label randomized clinical trial, 182 HSCT recipients were divided into three groups: Apixaban (n = 61, 2.5 mg two times a day), dalteparin (n = 59, 5000 IU daily), and unfractionated heparin (n =

Autoimmune Cytopenias Post Hematopoietic Stem Cell Transplantation in Pediatric Patients With Osteopetrosis and Other Nonmalignant Diseases.

Autoimmune cytopenia (AIC) is a rare complication post hematopoietic stem cell transplantation (HSCT), with a higher incidence in nonmalignant diseases. The etiology of post-HSCT AIC is poorly understood, and in many cases, the cytopenia is prolonged and refractory to treatment. Diagnosis of post-HSCT AIC may be challenging, and there is no consensus for a standard of care. In this retrospective study, we summarize our experience over the past five years with post-HSCT AIC in pediatric patients with osteopetrosis and other nonmalignant diseases. All pediatric patients who underwent HSCT for no

Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from two pediatric cases and review of literature.

BackgroundImmune-mediated cytopenias (AIC) are challenging complications following allogeneic hematopoietic stem cell transplantation (HSCT). While broad-acting immunosuppressive agents like corticosteroids are often standard of care, several novel therapies which target specific immunological pathways have recently been developed and provide hope for patients with steroid-refractory courses and may limit long-term toxicity. The successful off-label use of the plasma cell depleting anti-CD38 antibody daratumumab was published in several case reports, suggesting efficacy, i.e., in patients with

Clinical transplantation and tolerance: are we there yet?

Organ transplantation is not only considered as the last resort therapy but also as the treatment of choice for many patients with end-stage organ damage. Recipient-mediated acute or chronic immune response is the main challenge after transplant surgery. Nonspecific suppression of host immune system is currently the only method used to prevent organ rejection. Lifelong immunosuppression will cause significant side effects such as infections, malignancies, chronic kidney disease, hypertension and diabetes. This is more relevant in children who have a longer life expectancy so may receive longer

Cost analysis of childhood hematopoietic stem cell transplantation in Sichuan, China.

ObjectiveTo analyze the inpatient cost of hematopoietic stem cell transplantation (HSCT) in children, so as to support clinical decision-making.MethodsStudy population were children who received HSCT in a tertiary children's hospital (Sichuan, China) between 1st January 2020 and 31st December 2021. The median and interquartile range (IQR) of total cost at 100 days post transplantation were calculated. Subgroup analyses were conducted based on age, gender, transplantation types, and post-transplant complications. The cost differences between subgroups were analyzed to determine whether it had a

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the po

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… CD1d is an HLA class I-like molecule expressed in monocytes, macrophage dendritic cells, B cells, and thymocytes for glycolipid presentation [ 173 ]. However, the sufficiency of CD1d for iNKT cells to recognize senescent cells remains uncertain. … CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes. Immunology, 100:37-47. [174] Rowan AG, Ponnusamy K, Ren H, Taylor GP, Cook LBM, Karadimitris A (2023). CAR-iNKT cells targeting clonal TCRVβ chains as a precise strategy to treat T cell lymphoma. …

Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea.

Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell