{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T04:15:41Z","timestamp":1769314541268,"version":"3.49.0"},"reference-count":194,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CRIS Cancer Foundation"},{"name":"Fundaci\u00f3n Mari Paz Jim\u00e9nez Casado"},{"name":"Fundaci\u00f3n La Sonrisa de Alex"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune system against cancer has improved the survival rates dramatically in certain cancer types. Natural killer (NK) cells are a heterogeneous group of innate effector cells that possess numerous antitumor effects, such as cytolysis and cytokine production. Pediatric sarcoma cells have been shown to be especially susceptible to NK-cell-mediated killing. NK-cell adoptive therapy confers numerous advantages over T-cell adoptive therapy, including a good safety profile and a lack of major histocompatibility complex restriction. NK-cell immunotherapy has the potential to be a new therapy for pediatric malignant bone tumors. In this manuscript, we review the general characteristics of osteosarcoma and Ewing sarcoma, discuss the long-term effects of sarcoma treatment on bones, and the barriers to effective immunotherapy in bone sarcomas. We then present the laboratory and clinical studies on NK-cell immunotherapy for pediatric malignant bone tumors. We discuss the various donor sources and NK-cell types, the engineering of NK cells and combinatorial treatment approaches that are being studied to overcome the current challenges in adoptive NK-cell therapy, while suggesting approaches for future studies on NK-cell immunotherapy in pediatric bone tumors.<\/jats:p>","DOI":"10.3390\/ijms24098324","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T03:34:53Z","timestamp":1683516893000},"page":"8324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-3325","authenticated-orcid":false,"given":"Halin","family":"Bareke","sequence":"first","affiliation":[{"name":"Translational Research Group in Pediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adri\u00e1n","family":"Ib\u00e1\u00f1ez-Navarro","sequence":"additional","affiliation":[{"name":"Translational Research Group in Pediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-0614","authenticated-orcid":false,"given":"Pilar","family":"Guerra-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Gonz\u00e1lez P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Rubio-Aparicio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Plaza L\u00f3pez de Sabando","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Sastre-Urgelles","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo Jos\u00e9","family":"Ortiz-Cruz","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Traumatology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-9195","authenticated-orcid":false,"given":"Antonio","family":"P\u00e9rez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Translational Research Group in Pediatric Oncology, Haematopoietic Transplantation and Cell Therapy, Hospital La Paz Institute for Health Research, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Department of Pediatric Hemato-Oncology, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"School of Medicine, Autonomous University of Madrid, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(17)30186-9","article-title":"International incidence of childhood cancer, 2001\u20132010: A population-based registry study","volume":"18","author":"Colombet","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1126\/science.aaw3535","article-title":"The genomic landscape of pediatric cancers: Implications for diagnosis and treatment","volume":"363","author":"Biegel","year":"2019","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s10555-019-09836-y","article-title":"Compare and contrast: Pediatric cancer versus adult malignancies","volume":"38","author":"Kattner","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fonc.2013.00230","article-title":"Understanding the Biology of Bone Sarcoma from Early Initiating Events through Late Events in Metastasis and Disease Progression","volume":"3","author":"Zhu","year":"2013","journal-title":"Front. 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