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

Gabirel Astarloa-Pando¹Victor Sandá¹Ainhoa Amarilla-Irusta¹Ainara Lopez-Pardo¹Itxaso San Juan¹Ainhoa Iturbe-Larrondo¹Raquel Pérez-Garay^1,2Silvia Pérez-Fernández³Borja Santos-Zorrozúa³Bárbara Manzanares-Martín⁴Carmen González⁵Alasne Uranga⁶Mercedes Rey⁷Marta Alonso⁸Elena Amutio⁹Juan J Mateos-Mazón⁹Juan C García-Ruiz⁹Olatz Zenarruzabeitia^1,10Laura Amo^1,11*Francisco Borrego^1,11*

• ¹Immunopathology Group, Biobizkaia Health Research Institute, Barakaldo, Spain
• ²Clinical Analysis Service, Cruces University Hospital (OSI Ezkerraldea-Enkarterri-Cruces), Barakaldo, Spain
• ³Scientific Coordination Facility, Biobizkaia Health Research Institute, Barakaldo, Spain
• ⁴Clinical Management Unit of Immunology and Allergy, Reina Sofia Hospital, Córdoba, Spain
• ⁵Biogipuzkoa Health Research Institute, Hematology and Hemotherapy Service, Donostia University Hospital, Donostia-San Sebastián, Spain
• ⁶Biogipuzkoa Health Research Institute, Hematology and Hemotherapy Service, Donostia University Hospital, Donositia-San Sebastián, Spain
• ⁷Biogipuzkoa Health Research Institute, Service of Immunology, Donostia University Hospital, Donostia-San Sebastián, Spain
• ⁸Regulation of the Immune System Group, Biobizkaia Health Research Institute, Immunology Service, Cruces University Hospital, Barakaldo, Spain
• ⁹Hematological Cancer Group, Biobizkaia Health Research Institute, Hematology and Hemotherapy Service, Cruces University Hospital, Barakaldo, Spain
• ¹⁰Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country, Leioa, Spain
• ¹¹Ikerbasque, Basque Foundation for Science, Bilbao, Spain

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.