Publications by authors named "A Marcais"
Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer.
Nat Rev Drug Discov
December 2024
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.
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.
Article Synopsis
- 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