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

Author(s):Show less -

de Figueiredo-Pontes, Lorena Lobo ^[1] ; Adamcova, Miroslava K. ^{[2, 3]} ; Grusanovic, Srdjan ^{[2, 3, 4]} ; Kuzmina, Maria ^{[2, 4]} ; Lopes, Izabela Aparecida ^[1] ; de Oliveira Costa, Amanda Fernandes ^[1] ; Zhang, Hong ^[5] ; Strnad, Hynek ^[6] ; Lee, Sanghoon ^[7] ; Moudra, Alena ^{[8, 9]} ; Jonasova, Anna T. ^{[8, 9]} ; Zidka, Michal ^{[10, 11]} ; Welner, Robert S. ^{[5, 12]} ; Tenen, Daniel G. ^{[13, 5]} ; Alberich-Jorda, Meritxell ^{[2, 3]}

Affiliation:Show less -

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Images Hematol & Clin Oncol, Hematol Div, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Czech Acad Sci, Dept Hematooncol, Inst Mol Genet, Prague 14200 - Czech Republic

^[3] Charles Univ Prague, Univ Hosp Motol, Fac Med 2, Dept Pediat Haematol & Oncol, Childhood Leukaemia, Prague 15006 - Czech Republic

^[4] Charles Univ Prague, Fac Sci, Prague 12800 - Czech Republic

^[5] Harvard Med Sch, Harvard Stem Cell Inst, Boston, MA 02115 - USA

^[6] Czech Acad Sci, Dept Genom & Bioinformat, Inst Mol Genet, Prague 14200 - Czech Republic

^[7] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 - USA

^[8] Charles Univ Prague, Fac Med 1, Dept Med 1, Dept Haematol, Prague 12000 - Czech Republic

^[9] Gen Univ Hosp, Prague 12000 - Czech Republic

^[10] Orthopaed Dept CLPA Mediterra, Prague 19000 - Czech Republic

^[11] Charles Univ Prague, Med Fac 3, Prague 10000 - Czech Republic

^[12] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 - USA

^[13] Natl Univ Singapore, Canc Sci Inst, Singapore 117599 - Singapore

• Document type: Journal article
• Source: STEM CELL REPORTS; v. 16, n. 8, p. 1999-2013, AUG 10 2021.
• Web of Science Citations: 0

Abstract

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 (IFNg) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNg 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. (AU)

• FAPESP's process: 15/21866-1 - Cytokine-mediated regulation of normal and neoplastic hematopoietic stem cells by natural killer cells
• Grantee: Lorena Lôbo de Figueiredo Pontes
• Support Opportunities: Research Grants - Young Investigators Grants