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Improved hematopoietic stem cell transplantation upon inhibition of natural killer cell-derived interferon-gamma

Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminat...

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Detalles Bibliográficos
Autores principales: Lobo de Figueiredo-Pontes, Lorena, Adamcova, Miroslava K., Grusanovic, Srdjan, Kuzmina, Maria, Aparecida Lopes, Izabela, Fernandes de Oliveira Costa, Amanda, Zhang, Hong, Strnad, Hynek, Lee, Sanghoon, Moudra, Alena, Jonasova, Anna T., Zidka, Michal, Welner, Robert S., Tenen, Daniel G., Alberich-Jorda, Meritxell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365098/
https://www.ncbi.nlm.nih.gov/pubmed/34242616
http://dx.doi.org/10.1016/j.stemcr.2021.06.008
Descripción
Sumario:Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminating residual neoplastic cells. However, the effect that donor innate immune cells may have on the donor HSCs has not been deeply explored. Here, we evaluate the influence of donor natural killer (NK) cells on HSC fate, concluded that NK cells negatively affect HSC frequency and function, and identified interferon-gamma (IFNγ) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNγ activity. Thus, our data suggest that suppression of inflammatory signals generated by donor innate immune cells can enhance engraftment and hematopoietic reconstitution during HSCT, which is particularly critical when limited HSC numbers are available and the risk of engraftment failure is high.