Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer
Abstract Background Natural killer (NK) cells are among the first immune cell populations to recover after autologous hematopoietic stem cell transplantation (autoHSCT ), yet their dynamic function in pediatric patients remains understudied. Investigating NK cell recovery could improve understanding...
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Nature Portfolio
2025-05-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00911-w |
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| author | Gabirel Astarloa-Pando Diego Polanco-Alonso Víctor Sandá Ane Orrantia Ainhoa Amarilla-Irusta Silvia Pérez-Fernández Raquel Pérez-Garay Arrate Sevilla Ainara Lopez-Pardo Aritz Tijero José J. Úriz Mercedes Rey Itziar Astigarraga Bárbara Manzanares-Martin Aitor Zarandona-Garai Naiara G. Bediaga Laura Amo Olatz Zenarruzabeitia Francisco Borrego |
| author_facet | Gabirel Astarloa-Pando Diego Polanco-Alonso Víctor Sandá Ane Orrantia Ainhoa Amarilla-Irusta Silvia Pérez-Fernández Raquel Pérez-Garay Arrate Sevilla Ainara Lopez-Pardo Aritz Tijero José J. Úriz Mercedes Rey Itziar Astigarraga Bárbara Manzanares-Martin Aitor Zarandona-Garai Naiara G. Bediaga Laura Amo Olatz Zenarruzabeitia Francisco Borrego |
| author_sort | Gabirel Astarloa-Pando |
| collection | DOAJ |
| description | Abstract Background Natural killer (NK) cells are among the first immune cell populations to recover after autologous hematopoietic stem cell transplantation (autoHSCT ), yet their dynamic function in pediatric patients remains understudied. Investigating NK cell recovery could improve understanding of post-autoHSCT immune reconstitution and optimize clinical outcomes. Methods We characterized NK cells in 13 children (male: 8; female: 5; age range: 3–11 years) with various tumors before and up to 6 months after autoHSCT. Multiparametric flow cytometry analyses and plasma cytokine level determinations were performed. In vitro experiments, including single-cell RNA sequencing, were conducted to elucidate post-autoHSCT changes in the NK cell repertoire using 8 adult healthy donors (male: 5; female: 3; age range: 25–62 years). Results Key findings highlight a transient decidual-like NK cell phenotype emerging early post-transplant. These cells are immature and activated, with increased inhibitory receptor expression and diminished activating receptor levels. This activated and decidual-like phenotype is characterized by elevated expression of CD56, CD9, CD49a, CD151, CD38, HLA-DR, and CD55. Plasma levels of several cytokines are associated with the observed changes in NK cells’ phenotype. In addition, in vitro experiments recapitulate the alterations observed in NK cells shortly after autoHSCT. Specifically, results demonstrate that the combination of IL-15 and TGF-β induces this distinctive phenotype on NK cells after autoHSCT. Finally, we observe a positive correlation between relapse and the percentage of CD56dim NK cells shortly after autoHSCT in our cohort of pediatric patients. Conclusions Altogether, our findings provide valuable insights into the physiopathology of NK cells during immune system reconstitution after autoHSCT and can potentially help in the management of cancer in children. |
| format | Article |
| id | doaj-art-d16eb707a2df41f38eeb7a7ca06fe541 |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-d16eb707a2df41f38eeb7a7ca06fe5412025-08-20T03:16:51ZengNature PortfolioCommunications Medicine2730-664X2025-05-015111610.1038/s43856-025-00911-wNatural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancerGabirel Astarloa-Pando0Diego Polanco-Alonso1Víctor Sandá2Ane Orrantia3Ainhoa Amarilla-Irusta4Silvia Pérez-Fernández5Raquel Pérez-Garay6Arrate Sevilla7Ainara Lopez-Pardo8Aritz Tijero9José J. Úriz10Mercedes Rey11Itziar Astigarraga12Bárbara Manzanares-Martin13Aitor Zarandona-Garai14Naiara G. Bediaga15Laura Amo16Olatz Zenarruzabeitia17Francisco Borrego18Immunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteBioinformatics, Biostatistics and Information Systems Platform, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteBiogipuzkoa Health Research Institute, Service of Pediatrics, Donostia University HospitalBiogipuzkoa Health Research Institute, Service of Immunology, Donostia University HospitalPediatric Oncology Group, Department of Pediatrics, Biobizkaia Health Research Institute, Cruces University HospitalMaimónides Biomedical Research Institute of Córdoba (IMIBIC), Immunology and Allergy Department of Reina Sofía University Hospital and Transfusion, Tissue and Cells Centre (CTTC)Bioinformatics, Biostatistics and Information Systems Platform, Biobizkaia Health Research InstituteBioinformatics, Biostatistics and Information Systems Platform, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteImmunopathology Group, Biobizkaia Health Research InstituteAbstract Background Natural killer (NK) cells are among the first immune cell populations to recover after autologous hematopoietic stem cell transplantation (autoHSCT ), yet their dynamic function in pediatric patients remains understudied. Investigating NK cell recovery could improve understanding of post-autoHSCT immune reconstitution and optimize clinical outcomes. Methods We characterized NK cells in 13 children (male: 8; female: 5; age range: 3–11 years) with various tumors before and up to 6 months after autoHSCT. Multiparametric flow cytometry analyses and plasma cytokine level determinations were performed. In vitro experiments, including single-cell RNA sequencing, were conducted to elucidate post-autoHSCT changes in the NK cell repertoire using 8 adult healthy donors (male: 5; female: 3; age range: 25–62 years). Results Key findings highlight a transient decidual-like NK cell phenotype emerging early post-transplant. These cells are immature and activated, with increased inhibitory receptor expression and diminished activating receptor levels. This activated and decidual-like phenotype is characterized by elevated expression of CD56, CD9, CD49a, CD151, CD38, HLA-DR, and CD55. Plasma levels of several cytokines are associated with the observed changes in NK cells’ phenotype. In addition, in vitro experiments recapitulate the alterations observed in NK cells shortly after autoHSCT. Specifically, results demonstrate that the combination of IL-15 and TGF-β induces this distinctive phenotype on NK cells after autoHSCT. Finally, we observe a positive correlation between relapse and the percentage of CD56dim NK cells shortly after autoHSCT in our cohort of pediatric patients. Conclusions Altogether, our findings provide valuable insights into the physiopathology of NK cells during immune system reconstitution after autoHSCT and can potentially help in the management of cancer in children.https://doi.org/10.1038/s43856-025-00911-w |
| spellingShingle | Gabirel Astarloa-Pando Diego Polanco-Alonso Víctor Sandá Ane Orrantia Ainhoa Amarilla-Irusta Silvia Pérez-Fernández Raquel Pérez-Garay Arrate Sevilla Ainara Lopez-Pardo Aritz Tijero José J. Úriz Mercedes Rey Itziar Astigarraga Bárbara Manzanares-Martin Aitor Zarandona-Garai Naiara G. Bediaga Laura Amo Olatz Zenarruzabeitia Francisco Borrego Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer Communications Medicine |
| title | Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer |
| title_full | Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer |
| title_fullStr | Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer |
| title_full_unstemmed | Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer |
| title_short | Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer |
| title_sort | natural killer cells adopt an activated and decidual like phenotype after autologous hematopoietic stem cell transplantation in children with cancer |
| url | https://doi.org/10.1038/s43856-025-00911-w |
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