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.

Department of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences Prague 142 00 Czech Republic

Department of Hemato oncology Institute of Molecular Genetics of the Czech Academy of Sciences Prague 142 00 Czech Republic; Childhood Leukaemia Investigation Prague Department of Pediatric Haematology and Oncology 2nd Faculty of Medicine Charles University Prague University Hospital Motol Prague 150 06 Czech Republic

Department of Hemato oncology Institute of Molecular Genetics of the Czech Academy of Sciences Prague 142 00 Czech Republic; Childhood Leukaemia Investigation Prague Department of Pediatric Haematology and Oncology 2nd Faculty of Medicine Charles University Prague University Hospital Motol Prague 150 06 Czech Republic; Faculty of Science Charles University Prague 128 00 Czech Republic

Department of Hemato oncology Institute of Molecular Genetics of the Czech Academy of Sciences Prague 142 00 Czech Republic; Faculty of Science Charles University Prague 128 00 Czech Republic

Department of Medicine Department of Haematology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague 120 00 Czech Republic

Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Harvard Stem Cell Institute Harvard Medical School Boston MA 02115 USA

Harvard Stem Cell Institute Harvard Medical School Boston MA 02115 USA; Cancer Science Institute National University of Singapore Singapore 117599 Singapore

Harvard Stem Cell Institute Harvard Medical School Boston MA 02115 USA; Department of Medicine Division Hematology Oncology University of Alabama at Birmingham Birmingham AL 35294 USA

Hematology Division Department of Medical Images Hematology and Clinical Oncology Ribeirão Preto Medical School University of São Paulo Ribeirão Preto SP 14048 900 Brazil

Orthopaedic Department CLPA Mediterra Prague 190 00 Czech Republic; 3 Medical Faculty Charles University Prague 100 00 Czech Republic

Stem Cell Reports. 2022 Mar 8;17(3):443-445. doi: 10.1016/j.stemcr.2022.02.006. PubMed

Stem Cell Reports. 2022 Mar 8;17(3):446-447. doi: 10.1016/j.stemcr.2022.02.007. PubMed

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