# Dynamics of NK cell subsets following autologous hematopoietic stem cell transplantation in adult oncologic patients

**Authors:** Gabirel Astarloa-Pando, Victor Sandá, Ainhoa Amarilla-Irusta, Ainara Lopez-Pardo, Itxaso San Juan, Ainhoa Iturbe-Larrondo, Raquel Pérez-Garay, Silvia Pérez-Fernández, Borja Santos-Zorrozúa, Bárbara Manzanares-Martín, Raquel Bernardo, Carmen González, Alasne Uranga, Mercedes Rey, Marta Alonso, Elena Amutio, Juan J. Mateos-Mazón, Juan C. García-Ruiz, Olatz Zenarruzabeitia, Laura Amo, Francisco Borrego

PMC · DOI: 10.3389/fimmu.2025.1629118 · Frontiers in Immunology · 2025-10-07

## TL;DR

This study explores how natural killer (NK) cells change after stem cell transplants in cancer patients, revealing a temporary immature and activated state that could impact recovery and cancer outcomes.

## Contribution

The study identifies a transient decidual-like and activated NK cell phenotype post-transplant and links it to potential clinical implications.

## Key findings

- NK cells transiently acquire a decidual-like phenotype with increased CD56, CD9, CD49a, CD151, CD38, and HLA-DR expression after autoHSCT.
- Phenotypic changes in NK cells correlate with plasma cytokine levels and may modulate NK cell function.
- In NHL patients, NK cell maturation status correlates with progression-free survival.

## Abstract

Early immune reconstitution following autologous hematopoietic stem cell transplantation (autoHSCT) is associated with improved outcome in various cancers. Natural killer (NK) cells are the first lymphocyte subset to recover post-autoHSCT and play a crucial role in antitumor immunity. In this study, we have performed an in-depth characterization of NK cells in adult patients with different hematological malignancies. Our results revealed that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, displayed a more immature and activated state, and exhibited an upregulation of inhibitory receptors and a downregulation of activating receptors. This decidual-like and activated phenotype was characterized by increased expression of CD56, CD9, CD49a, CD151, CD38 and HLA-DR. Additionally, we assessed plasma cytokine levels and identified associations between cytokine concentrations and NK cell phenotypic changes. In vitro experiments suggested that these phenotype alterations could modulate NK cell function. Finally, in patients with non-Hodgkin lymphoma (NHL), we observed a correlation between NK cell maturation status and progression-free survival. Collectively, our findings provide valuable insights into NK cell dynamics during immune reconstitution following autoHSCT and may inform of strategies for improving patients’ management.

## Linked entities

- **Proteins:** NCAM1 (neural cell adhesion molecule 1), CD9 (CD9 molecule), ITGA1 (integrin subunit alpha 1), CD151 (CD151 molecule (Raph blood group)), CD38 (CD38 molecule)
- **Diseases:** non-Hodgkin lymphoma (MONDO:0018908)

## Full-text entities

- **Genes:** CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, CD151 (CD151 molecule (Raph blood group)) [NCBI Gene 977] {aka EBS7, GP27, MER2, PETA-3, RAPH, SFA1}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, ITGA1 (integrin subunit alpha 1) [NCBI Gene 3672] {aka CD49a, VLA1}
- **Diseases:** oncologic (MESH:D000072716), cancers (MESH:D009369), NHL (MESH:D008228), hematological malignancies (MESH:D019337)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12537779/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12537779/full.md

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Source: https://tomesphere.com/paper/PMC12537779