ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1625437
This article is part of the Research TopicInflammation, Immunity, and Cancer: New Pathways Towards Therapeutic InnovationView all 5 articles
Distinct NK Cell Function and Gene Expression in Children with Acute Lymphoblastic Leukemia in Remission Before and After Acute Exercise: An Exploratory Study
Provisionally accepted
Abel Plaza-Florido1*
Martin Perlsteyn1
Fadia Haddad1
Dan M Cooper1,2Ronen Bar- Yoseph1,3
Alejandro Lucia4,5Shlomit Radom-Aizik1*- 1Research Center for Exercise Medicine and Sleep/Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, California, USA., Irvine, United States
- 2University of California Irvine, Institute for Clinical Translational Science (ICTS), Irvine, United States
- 3Pediatric Pulmonary Institute, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel, Haifa, Israel
- 4Department of Sport Sciences. Faculty of Medicine, Health and Sports. Universidad Europea de Madrid, Madrid, Spain, Madrid, Spain
- 5Physical Exercise and Pediatric Cancer Research Group, Research Institute of the Hospital 12 de Octubre (‘imas12’), Madrid, Spain, Madrid, Spain
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Brief bouts of exercise mobilize natural killer (NK) cells and influence their function and gene expression in adults. However, little is known about these effects in children with acute lymphoblastic leukemia (ALL) in remission. This study investigated the effect of acute exercise on NK gene expression and cytotoxic activity (NKCA) in children with ALL in remission. Methods: Nine B-cell ALL children in remission and 9 age-and sex-matched healthy controls (14.8±1 and 15±1 y/o, respectively; 2 girls per group) performed an acute exercise session consisting of eight 2-min bouts of cycle ergometry at 60% of peak work rate (71±2% of peak oxygen uptake) interspersed with 1-min rest intervals. Circulating NK-cell gene expression profile (RNA-seq) and NKCA (in vitro assay) were studied before and after the exercise session. Results: At baseline, 284 genes were differently expressed in children with ALL compared to controls, and 179 genes were differently altered by acute exercise in the ALL group (p<0.01). At baseline, nine gene pathways related to NK cell function were affected, while following exercise, 28 pathways associated with inflammatory response and cancer were impacted (FDR<0.05). NKCA following IL-2 stimulation was lower both at baseline (p<0.05) and after exercise (p=0.09) in ALL compared to controls. The impaired activity was partially mitigated following exercise but remained lower in ALL compared to controls. Acute exercise may improve NK cell function in ALL children in remission and has the potential to be used as adjunctive therapy in ALL. The differential gene expression response to exercise suggests that NK cells in ALL may adopt a different molecular strategy to fight infections or tumors.
Keywords: fitness, physical activity, omics, Immune function, Cancer
Received: 08 May 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Plaza-Florido, Perlsteyn, Haddad, Cooper, Bar- Yoseph, Lucia and Radom-Aizik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Abel Plaza-Florido, Research Center for Exercise Medicine and Sleep/Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, California, USA., Irvine, United States
Shlomit Radom-Aizik, Research Center for Exercise Medicine and Sleep/Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, California, USA., Irvine, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.