Publications by authors named "Marcais A"

Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.

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The importance of metabolic pathways in regulating immune responses is now well established, and a mapping of the bioenergetic metabolism of different immune cell types is under way. CD8 T cells and natural killer (NK) cells contribute to cancer immunosurveillance through their cytotoxic functions and secretion of cytokines and chemokines, complementing each other in target recognition mechanisms. Several immunotherapies leverage these cell types by either stimulating their activity or redirecting their specificity against tumour cells.

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  • The study examines the blood-related characteristics and overall prognosis of 127 patients with telomere biology disorders (TBD) who were diagnosed after age 15, highlighting a lack of data on this topic.
  • At diagnosis, significant haematological issues were present in nearly 76% of patients, with bone marrow failure (BMF) being the most common, affecting 46.5% of the cases, while some patients also developed additional complications over time.
  • The findings suggest that BMF patients tend to be younger and have a better survival rate compared to those with higher-risk blood cancers, indicating TBD as a complex multi-organ disease needing further research on its evolutionary nature and outcomes.
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Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute myeloid and lymphoid leukemia (AML and ALL) and for myelodysplastic syndroms (MDS). More and more patients are eligible for allo-HCT over the years and for many of them, only reduced intensity conditioning is possible, which is associated with a higher risk of relapse. Knowledge and biotechnology allow us to better identify diseases at very high risk of relapse and to measure residual disease before allo-HCT.

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  • NK cells often lose their function during tumor development, but the reasons for this are not fully understood.
  • In mouse lymphoma models, the activation of NK cells led to changes resembling T cell exhaustion, including the expression of immune checkpoint proteins, but dysfunction occurred only in the activated NK cell group.
  • Importantly, NK cell dysfunction can be reversed by stopping the stimulation and is positively influenced by interleukin-15, indicating that the dysfunction is a dynamic and reversible process not directly linked to immune checkpoint protein expression.
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  • The study examines outcomes of 67 patients (average age 20.6 years) who underwent their first allogeneic hematopoietic stem cell transplant (HSCT) due to GATA2 deficiency across 21 centers in June 2022, showing varied indications for the transplant.
  • The findings reveal significant rates of acute graft versus host disease (GvHD) and chronic GvHD; the incidence of relapses was low, with overall survival rates at 1 and 5 years being 83% and 72%, respectively.
  • The analysis highlights that monitoring bone marrow for clonal evolution is crucial to initiate HSCT before the development of excessive blasts, noting that factors like earlier years of HSCT and certain
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In Europe, most HTLV-1-infected individuals originate from highly endemic regions such as West Indies, sub-Saharan Africa, and South America. The only genuine endemic region for HTLV-1 in Europe is Romania where ATL series have been reported among Romanian patients. Our objective is to better understand the origin of this endemic focus based on a study of the genetic diversity of HTLV-1 in Romanians.

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  • HSCT is the only curative treatment for patients with short telomere syndromes and severe bone marrow failure or myeloid malignancies, but the effectiveness is influenced by their sensitivity to the conditioning regimen.
  • In a study involving adults and adolescents treated with an alemtuzumab-based regimen, outcomes showed a low 2-year graft rejection-free survival (GRFS) rate for those with myeloid malignancies (20%) compared to other patients (57%).
  • While the overall 2-year overall survival (OS) was quite favorable at 66%, the findings suggest that alternative treatment strategies may be necessary for patients with myeloid malignancies.
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  • Hexokinases are enzymes that initiate the breakdown of glucose, with a switch from liver glucokinase (GCK) to HK2 occurring in liver cancer progression.
  • The study reveals that HK2 expression in liver cancer cells helps these cells resist destruction by Natural Killer (NK) cells, due to its binding to mitochondria.
  • This HK2-mitochondrial interaction reduces the activity of certain caspases involved in cell death and enhances resistance to signals that would typically trigger apoptosis, helping cancer cells escape the immune response.
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Chronic Granulomatosis Disease (CGD) is an inherited immune deficiency due to a mutation in the genes coding for the subunits of the NADPH oxidase enzyme that affects the oxidative capacity of phagocytic cells. It is characterized by increased susceptibility to bacterial and fungal infections, particularly Aspergillus, as well as complications associated with hyperinflammation and granulomatous tissue infiltration. There exist two types of frequently encountered pulmonary manifestations: (1) due to their being initially pauci-symptomatic, possibly life-threatening infectious complications are often discovered at a late stage.

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The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy.

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  • - CD8+ T cells and Natural Killer (NK) cells are crucial for fighting off viral infections and cancer, and their effectiveness relies on various signals from their environment, including cytokines and nutrients.
  • - The mechanistic target of rapamycin (mTOR) serves as a central regulator of cellular growth and metabolism, playing a key role in the maturation of these immune cells.
  • - Recent research is focusing on how mTOR is activated in primary immune cells (instead of cell lines) and how understanding this signaling can enhance immunotherapy strategies for treating cancer.
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Complement activation has shown a role in murine models of graft-versus-host disease (GVHD) and in endothelial complications after allogeneic hematopoietic cell transplantation (allo-HSCT). However, its impact on post-transplant outcomes has not been so far fully elucidated. Here, we conducted a prospective multicentric trial (NCT01520623) performing serial measurements of complement proteins, regulators, and CH50 activity for 12 weeks after allo-HSCT in 85 patients receiving a myeloablative conditioning (MAC) regimen for various hematological malignancies.

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Background: Adult T-cell leukemia/lymphoma (ATL), one of the most aggressive cancers in the world, occurs in 5% of the 10 million people living with HTLV-1 worldwide. French Guiana, a French overseas territory in South America, is one of the highest endemic areas of HTLV-1 worldwide. Here, we describe the demographic and clinical characteristics and outcome of ATL in this area.

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Background: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs.

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  • Metagenomic next-generation sequencing (mNGS) was utilized to study patients with primary or secondary immune deficiencies (PIDs and SIDs) who exhibited immunopathological issues.
  • The study involved 30 symptomatic and 59 asymptomatic patients, with mNGS revealing Aichi virus (AiV) in tissue from some infected patients, confirming the potential link between AiV and immunodysregulation.
  • Results showed that AiV was associated with significant clinical symptoms, including multiorgan involvement, and symptoms improved after treatment, supporting the idea that AiV may be a causal factor in these patients.
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  • Autosomal recessive PRKCD deficiency is linked to systemic lupus erythematosus, but its specific mechanisms are not well understood.
  • Researchers created a mouse model with the Prkcd G510S mutation to study the disease, which mimics human symptoms and shows a shortened lifespan.
  • The study found that this mutation affects B cell activation through the PI3K/mTOR pathway, leading to autoimmune symptoms that improve with rapamycin treatment, highlighting the pathway's role in PRKCD-related autoimmunity and reduced NK cell levels contributing to viral infection susceptibility.
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Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been formerly re-evaluated. We report here the outcome of patients with initial CNS involvement included in the pediatric-inspired prospective randomized GRAALL-2005 study. Between 2006 and 2014, 784 adult patients (aged 18-59 years) with newly diagnosed Philadelphia-negative ALL were included, of whom 55 (7%) had CNS involvement.

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  • Late relapse (LR) after a special blood stem cell treatment for leukemia happens in about 4.5% of patients and is studied to find out how well they do after this happens.
  • A study looked at 7,582 patients who had the treatment, and 319 of them had late relapses, mostly after about 38 months.
  • The chances of living longer after a late relapse were about 19.9 months, with many patients getting better after a second treatment.
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