{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:29:54Z","timestamp":1788348594441,"version":"build-2803163510"},"reference-count":108,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: High-risk neuroblastoma (HR-NB) is a major cause of cancer-related death among children. The review aims to discuss various biochemical and genetic traits of neuroblastoma (NB) used for the potential of cell-based therapies. Methods: A comprehensive search was performed through MEDLINE, PubMed, Scopus, and ScienceDirect using various combinations of \u201cneuroblastoma\u201d, \u201ctumor microenvironment (TME)\u201d, \u201cimmune cells\u201d, \u201cnon-immune cells\u201d, \u201chematopoietic stem cell transplantation (HSCT)\u201d, \u201cautologous stem cell transplantation (ASCT)\u201d, \u201cnatural killer cells (NK)\u201d, \u201cchimeric antigen receptor T cells (CAR-T)\u201d, \u201cCAR-NKT\u201d, \u201ctumor infiltrating lymphocytes (TIL)\u201d, \u201cbioinformatics\u201d, and \u201cneuro-antigens\u201d in the published papers over the last decade. Reviews, systematic reviews, and clinical trials related to children\u2019s NB were selected. The final set included 106 articles of interest. Results: Recent studies have shown that TME is crucial in determining the malignancy, immune evasion, and drug resistance of NB. Innate immune or non-immune cells play important roles in shaping the NB TME. Depleting or reprogramming TME factors can improve the effectiveness of immunotherapy. A number of clinical trials have studied and showed feasibility of using ASCT, NK cells, CAR-T, and CAR-NKT cells in the adoptive therapy for HR-NB. However, an unambiguous evaluation of the effectiveness of cell-based technologies in the HR-NB therapy is still complicated due to the lack of large randomized trials. Conclusions: The reported small and non-randomized studies that demonstrated controversial results cannot prove, undoubtedly, the promising potential of the cell-based technologies including ASCT, NKs, CAR-T, and CAR-NKT cells. Further randomized clinical trials, using the same treatment, will help determine the role in the multimodal treatment for HR-NB.<\/jats:p>","DOI":"10.3390\/cancers18071079","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:48:41Z","timestamp":1774532921000},"page":"1079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor Microenvironment in Neuroblastoma and Immunotherapeutic Approaches: Towards More Effective Treatment"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-3158","authenticated-orcid":false,"given":"Irina Zh.","family":"Shubina","sequence":"first","affiliation":[{"name":"FSBI \u201cN.N. Blokhin National Medical Research Center of Oncology\u201d of the Ministry of Health of Russia, Kashirskoye sh. 24, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-1634","authenticated-orcid":false,"given":"Chi-Bao","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-1072","authenticated-orcid":false,"given":"Truc Ly","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly P.","family":"Kazantsev","sequence":"additional","affiliation":[{"name":"FSBI \u201cN.N. Blokhin National Medical Research Center of Oncology\u201d of the Ministry of Health of Russia, Kashirskoye sh. 24, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6134-9453","authenticated-orcid":false,"given":"Duy Khang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-2927","authenticated-orcid":false,"given":"Quynh Giang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khang Thinh","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-223X","authenticated-orcid":false,"given":"Natalya A.","family":"Burlaka","sequence":"additional","affiliation":[{"name":"FSBI \u201cN.N. Blokhin National Medical Research Center of Oncology\u201d of the Ministry of Health of Russia, Kashirskoye sh. 24, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay Yu.","family":"Sokolov","sequence":"additional","affiliation":[{"name":"SBHI S.P. Botkin Hospital, 2nd Botkinsky pr-d, 5, Moscow 125284, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill I.","family":"Kirgizov","sequence":"additional","affiliation":[{"name":"FSBI \u201cN.N. Blokhin National Medical Research Center of Oncology\u201d of the Ministry of Health of Russia, Kashirskoye sh. 24, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana R.","family":"Varfolomeeva","sequence":"additional","affiliation":[{"name":"FSBI \u201cN.N. Blokhin National Medical Research Center of Oncology\u201d of the Ministry of Health of Russia, Kashirskoye sh. 24, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Kiselevskiy","sequence":"additional","affiliation":[{"name":"FSBI \u201cN.N. Blokhin National Medical Research Center of Oncology\u201d of the Ministry of Health of Russia, Kashirskoye sh. 24, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.yapd.2011.03.011","article-title":"Neuroblastoma","volume":"58","author":"Colon","year":"2011","journal-title":"Adv. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.hoc.2009.11.011","article-title":"Neuroblastoma: Biology, Prognosis, and Treatment","volume":"24","author":"Park","year":"2010","journal-title":"Hematol.\/Oncol. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.canlet.2015.11.017","article-title":"More than the genes, the tumor microenvironment in neuroblastoma","volume":"380","author":"Borriello","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Liu, K.X., and Joshi, S. (2020). \u201cRe-educating\u201d Tumor Associated Macrophages as a Novel Immunotherapy Strategy for Neuroblastoma. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01947"},{"key":"ref_5","unstructured":"Challagundla, K.B. (2026, February 02). Neuroblastoma, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK448111\/."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Blavier, L., Yang, R.-M., and DeClerck, Y.A. (2020). The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives. Cancers, 12.","DOI":"10.3390\/cancers12102912"},{"key":"ref_7","first-page":"305","article-title":"Exploring and Targeting the Tumor Immune Microenvironment of Neuroblastoma","volume":"3","author":"Masih","year":"2021","journal-title":"J. Cell. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e15356","DOI":"10.1002\/advs.202415356","article-title":"Systematic Targeting of GD2-Positive Neuroblastoma Tumors With a Photooncolytic Phage Nanovector Platform","volume":"12","author":"Zadran","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e8017","DOI":"10.7717\/peerj.8017","article-title":"Cellular components in tumor microenvironment of neuroblastoma and the prognostic value","volume":"7","author":"Zhong","year":"2019","journal-title":"PeerJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1200\/JCO.2011.40.9169","article-title":"Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma","volume":"30","author":"Asgharzadeh","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/path.4769","article-title":"Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development","volume":"240","author":"Hashimoto","year":"2016","journal-title":"J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1158\/0008-5472.CAN-12-2353","article-title":"Critical Role of STAT3 in IL-6\u2013Mediated Drug Resistance in Human Neuroblastoma","volume":"73","author":"Ara","year":"2013","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1186\/s13046-023-02913-9","article-title":"Targeting the myeloid microenvironment in neuroblastoma","volume":"42","author":"Stip","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1158\/1078-0432.CCR-09-0223","article-title":"HIF-1\u03b1 and HIF-2\u03b1 Are Differentially Regulated In vivo in Neuroblastoma: High HIF-1\u03b1 Correlates Negatively to Advanced Clinical Stage and Tumor Vascularization","volume":"15","author":"Noguera","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s00262-013-1466-y","article-title":"Lenalidomide overcomes suppression of human natural killer cell anti-tumor functions by neuroblastoma microenvironment-associated IL-6 and TGF\u03b21","volume":"62","author":"Xu","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bottino, C., Dondero, A., Bellora, F., Moretta, L., Locatelli, F., Pistoia, V., Moretta, A., and Castriconi, R. (2014). Natural Killer Cells and Neuroblastoma: Tumor Recognition, Escape Mechanisms, and Possible Novel Immunotherapeutic Approaches. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00056"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5992","DOI":"10.1038\/s41467-020-19781-y","article-title":"Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma","volume":"11","author":"Melaiu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jss.2020.03.059","article-title":"Immune Checkpoint Inhibition Followed by Tumor Infiltration of Dendritic Cells in Murine Neuro-2a Neuroblastoma","volume":"253","author":"Inoue","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Polychronopoulos, P.A., Bedoya-Reina, O.C., and Johnsen, J.I. (2024). The Neuroblastoma Microenvironment, Heterogeneity and Immunotherapeutic Approaches. Cancers, 16.","DOI":"10.3390\/cancers16101863"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Joshi, S. (2020). Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions. Cancers, 12.","DOI":"10.3390\/cancers12082057"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100657","DOI":"10.1016\/j.xcrm.2022.100657","article-title":"The immune cell atlas of human neuroblastoma","volume":"3","author":"Verhoeven","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41392-021-00670-9","article-title":"Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mao, C., Poimenidou, M., and Craig, B.T. (2024). Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma. Cancers, 16.","DOI":"10.3390\/cancers16162865"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/(SICI)1097-0142(19990715)86:2<349::AID-CNCR20>3.0.CO;2-Y","article-title":"Terminology and morphologic criteria of neuroblastic tumors: Recommendations by the International Neuroblastoma Pathology Committee","volume":"86","author":"Shimada","year":"1999","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/modpathol.2009.52","article-title":"Presence of cancer-associated fibroblasts inversely correlates with Schwannian stroma in neuroblastoma tumors","volume":"22","author":"Zeine","year":"2009","journal-title":"Mod. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1177\/10935266211039200","article-title":"Collagen XI Alpha 1 (COL11A1) Expression in the Tumor Microenvironment Drives Neuroblastoma Dissemination","volume":"25","author":"Truong","year":"2021","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_27","first-page":"289","article-title":"Study on collagen type 11A1 and collagen type 4A1 expression in neuroblastoma","volume":"2","author":"Luu","year":"2021","journal-title":"VNUHCM J. Health Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s12967-019-2058-1","article-title":"The role of collagen in cancer: From bench to bedside","volume":"17","author":"Xu","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Horwacik, I. (2022). The Extracellular Matrix and Neuroblastoma Cell Communication\u2014A Complex Interplay and Its Therapeutic Implications. Cells, 11.","DOI":"10.3390\/cells11193172"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1476-4598-9-35","article-title":"Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression","volume":"9","author":"Lam","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.actbio.2018.02.004","article-title":"A physiologically relevant 3D collagen-based scaffold\u2013neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models","volume":"70","author":"Curtin","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103624","DOI":"10.1016\/j.jtherbio.2023.103624","article-title":"Denatured collagen inhibits neuroblastoma tumor-sphere migration and growth via the LOX\/LOXL2\u2014FAK signaling pathway","volume":"115","author":"Bui","year":"2023","journal-title":"J. Therm. Biol."},{"key":"ref_33","first-page":"611","article-title":"Optimizing Fiber Laser Ablation for Enhancing the Tumor Microenvironment in Neuroblastoma","volume":"4","author":"Nguyen","year":"2023","journal-title":"VNUHCM J. Health Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nguyen, D.K., Nguyen, Q.G., Nguyen, T.Q., Bui, C.B., and Nguyen, S.B. (2025). Enhancing Immune Surveillance and Tumor Microenvironment Modulation in Neuroblastoma Through Thermal Laser Ablation via Single-Cell RNA Sequencing. 10th International Conference on the Development of Biomedical Engineering in Vietnam, Springer.","DOI":"10.1007\/978-3-031-90197-3_22"},{"key":"ref_35","unstructured":"ACSmaectASoCO (ASCO) (2025). Treating Neuroblastoma, American Cancer Society. Available online: https:\/\/www.cancer.org\/cancer\/types\/neuroblastoma\/treating.html."},{"key":"ref_36","unstructured":"National Cancer Institute (2026, February 02). FDA Approves First Therapy for High-Risk Neuroblastoma, Available online: https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2015\/dinutuximab-neuroblastoma."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10014","DOI":"10.1200\/JCO.2019.37.15_suppl.10014","article-title":"Randomized use of anti-GD 2 antibody dinutuximab beta (DB) long-term infusion with and without subcutaneous interleukin-2 (scIL-2) in high-risk neuroblastoma patients with relapsed and refractory disease: Results from the SIOPEN LTI-trial","volume":"37","author":"Lode","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/S1470-2045(18)30578-3","article-title":"Interleukin 2 with anti-GD2 antibody ch1418\/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1\/SIOPEN): A multicentre, randomised, phase 3 trial","volume":"19","author":"Ladenstein","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/pbc.26184","article-title":"Lack of immunocytological GD2 expression on neuroblastoma cells in bone marrow at diagnosis, during treatment, and at recurrence","volume":"64","author":"Volland","year":"2017","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Siebert, N., Troschke-Meurer, S., Marx, M., Zumpe, M., Ehlert, K., Gray, J., Garaventa, A., Manzitti, C., Ash, S., and Klingebiel, T. (2018). Impact of HACA on immunomodulation and treatment toxicity following ch14.18\/CHO long-term infusion with interleukin-2: Results from a SIOPEN phase 2 trial. Cancers, 10.","DOI":"10.3390\/cancers10100387"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s40272-021-00469-9","article-title":"Managing adverse events associated with dinutuximab beta treatment in patients with high-risk neuroblastoma: Practical guidance","volume":"23","author":"Barone","year":"2021","journal-title":"Paediatr. Drugs"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10013","DOI":"10.1200\/JCO.2019.37.15_suppl.10013","article-title":"Randomization of dose-reduced subcutaneous inter-leukin-2 (scIL2) in maintenance immunotherapy (IT) with anti-GD2 antibody dinutuximab beta (DB) long-term infusion (LTI) in front-line high-risk neuroblastoma patients: Early results from the HR-NBL1\/SIOPEN trial","volume":"37","author":"Ladenstein","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.bbmt.2016.11.022","article-title":"Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation","volume":"23","author":"Lucchini","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mora, J. (2022). Autologous Stem-Cell Transplantation for High-Risk Neuroblastoma: Historical and Critical Review. Cancers, 14.","DOI":"10.3390\/cancers14112572"},{"key":"ref_45","first-page":"CD011405","article-title":"High-dose chemotherapy followed by autologous haematopoietic cell transplantation for children, adolescents, and young adults with primary metastatic Ewing sarcoma","volume":"2021","author":"Haveman","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/sj.bmt.1703023","article-title":"High-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT) as salvage therapy for relapsed osteosarcoma","volume":"27","author":"Sauerbrey","year":"2001","journal-title":"Bone Marrow Transplant."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/a-1014-3250","article-title":"High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99","volume":"231","author":"Maxwell","year":"2019","journal-title":"Klin. P\u00e4diatrie"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/jama.2019.11642","article-title":"Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma","volume":"322","author":"Park","year":"2019","journal-title":"JAMA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S118","DOI":"10.1038\/bmt.2008.69","article-title":"28 years of high-dose therapy and SCT for neuroblastoma in Europe: Lessons from more than 4000 procedures","volume":"41","author":"Ladenstein","year":"2008","journal-title":"Bone Marrow Transplant."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/pbc.21784","article-title":"Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: A report from the Children\u2019s Oncology Group","volume":"52","author":"Park","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ladenstein, R., P\u00f6tschger, U., Valteau-Couanet, D., Luksch, R., Castel, V., Ash, S., Laureys, G., Brock, P., Michon, J.M., and Owens, C. (2020). Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1). Cancers, 12.","DOI":"10.3390\/cancers12020309"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3109\/07853890.2011.554430","article-title":"The role of natural killer cells in hematopoietic stem cell transplantation","volume":"44","author":"Tsirigotis","year":"2011","journal-title":"Ann. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e29663","DOI":"10.1002\/pbc.29663","article-title":"To transplant, or not to transplant? That is the question. A patient advocate evaluation of autologous stem cell transplant in neuroblastoma","volume":"69","author":"Bird","year":"2022","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_54","unstructured":"A Ratko, T., E Belinson, S., Brown, H.M., Noorani, H.Z., Chopra, R.D., Marbella, A., Samson, D.J., Bonnell, C.J., Ziegler, K.M., and Aronson, N. (2012). Hematopoietic Stem-Cell Transplantation in the Pediatric Population [Internet], Agency for Healthcare Research and Quality (US). Report No.: 12-EHC018-EF."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.1198687","article-title":"Innate or Adaptive Immunity? The Example of Natural Killer Cells","volume":"331","author":"Vivier","year":"2011","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1196\/annals.1322.008","article-title":"Immunogenicity of Human Neuroblastoma","volume":"1028","author":"Prigione","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1200\/JCO.21.01375","article-title":"Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated with Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A","volume":"40","author":"Furman","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1056\/NEJMoa0911123","article-title":"Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for Neuroblastoma","volume":"363","author":"Yu","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s12185-017-2379-x","article-title":"NK cell therapy after hematopoietic stem cell transplantation: Can we improve anti-tumor effect?","volume":"107","author":"Ciurea","year":"2018","journal-title":"Int. J. Hematol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1158\/1078-0432.CCR-18-1317","article-title":"Activated Natural Killer Cells in Combination with Anti-GD2 Antibody Dinutuximab Improve Survival of Mice after Surgical Resection of Primary Neuroblastoma","volume":"25","author":"Barry","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20971","DOI":"10.1038\/s41598-024-70958-7","article-title":"Phase I study of safety and efficacy of allogeneic natural killer cell therapy in relapsed\/refractory neuroblastomas post autologous hematopoietic stem cell transplantation","volume":"14","author":"Mohseni","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s00262-025-03990-9","article-title":"Ex vivo-expanded and activated haploidentical natural killer cells infusion before autologous stem cell transplantation in high-risk neuroblastoma: A phase I\/II pilot study","volume":"74","author":"Rostami","year":"2025","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e000176","DOI":"10.1136\/jitc-2019-000176","article-title":"Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial","volume":"8","author":"Nguyen","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/pbc.24030","article-title":"NK Cell immunotherapy for high-risk neuroblastoma relapse after haploidentical HSCT","volume":"59","author":"Kanold","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.bbmt.2017.07.011","article-title":"Consolidation Therapy for Newly Diagnosed Pediatric Patients with High-Risk Neuroblastoma Using Busulfan\/Melphalan, Autologous Hematopoietic Cell Transplantation, Anti-GD2 Antibody, Granulocyte-Macrophage Colony\u2013Stimulating Factor, Interleukin-2, and Haploidentical Natural Killer Cells","volume":"23","author":"Talleur","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6441","DOI":"10.1158\/1078-0432.CCR-17-0379","article-title":"A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent\/Refractory Neuroblastoma","volume":"23","author":"Federico","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1158\/1078-0432.CCR-21-1356","article-title":"Immunotherapy of Neuroblastoma: Facts and Hopes","volume":"28","author":"Anderson","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1056\/NEJMoa1709919","article-title":"Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia","volume":"378","author":"Park","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/nm.1882","article-title":"Virus-specific T cells engineered to coexpress tumor-specific receptors: Persistence and antitumor activity in individuals with neuroblastoma","volume":"14","author":"Pule","year":"2008","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6050","DOI":"10.1182\/blood-2011-05-354449","article-title":"Antitumor activity and long-term fate of chimeric antigen receptor\u2013positive T cells in patients with neuroblastoma","volume":"118","author":"Louis","year":"2011","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eabd6169","DOI":"10.1126\/scitranslmed.abd6169","article-title":"Antitumor activity without on-target off-tumor toxicity of GD2\u2013chimeric antigen receptor T cells in patients with neuroblastoma","volume":"12","author":"Straathof","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1007\/s00432-021-03839-5","article-title":"GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and\/or recurrent neuroblastoma in pediatric patients","volume":"148","author":"Yu","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/s41591-025-03513-0","article-title":"Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma","volume":"31","author":"Li","year":"2025","journal-title":"Nat. Med."},{"key":"ref_74","unstructured":"Li, C.H., Sharma, S., Heczey, A.A., Woods, M.L., Steffin, D.H.M., Louis, C.U., Grilley, B.J., Thakkar, S.G., Wu, M., and Wang, T. (2024). Eighteen-year survival after GD2-directed Chimeric Antigen Receptor-Modified Immune Effector Cell Treatment for Neuroblastoma. Res. Sq., preprint."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/ejh.13170","article-title":"NKT cells\u2014New players in CAR cell immunotherapy?","volume":"101","author":"Kriegsmann","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/s41591-020-1074-2","article-title":"Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: An interim analysis","volume":"26","author":"Heczey","year":"2020","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1056\/NEJMoa2210859","article-title":"GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma","volume":"388","author":"Caruana","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s40164-025-00711-x","article-title":"Novel tumor-infiltrating lymphocytes therapy in solid tumors: Latest updates from 2025 ASCO annual meeting","volume":"14","author":"Ma","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Frosch, J., Leontari, I., and Anderson, J. (2021). Combined Effects of Myeloid Cells in the Neuroblastoma Tumor Microenvironment. Cancers, 13.","DOI":"10.3390\/cancers13071743"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e23618","DOI":"10.4161\/onci.23618","article-title":"The microenvironment of human neuroblastoma supports the activation of tumor-associated T lymphocytes","volume":"2","author":"Carlson","year":"2013","journal-title":"OncoImmunology"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Olle Hurtado, M.O., Wolbert, J., Fisher, J., Flutter, B., Stafford, S., Barton, J., Jain, N., Barone, G., Majani, Y., and Anderson, J. (2019). Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216373"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6758","DOI":"10.1158\/1078-0432.CCR-12-1177","article-title":"Specific Lymphocyte Subsets Predict Response to Adoptive Cell Therapy Using Expanded Autologous Tumor-Infiltrating Lymphocytes in Metastatic Melanoma Patients","volume":"18","author":"Radvanyi","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"16078","DOI":"10.1038\/nrdp.2016.78","article-title":"Neuroblastoma","volume":"2","author":"Matthay","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e31831","DOI":"10.1002\/pbc.31831","article-title":"Accelerating Drug Development for Neuroblastoma: Consensus Statement from the Third Neuroblastoma Drug Development Strategy Forum","volume":"72","author":"DuBois","year":"2025","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1200\/JCO.2014.59.4648","article-title":"Advances in Risk Classification and Treatment Strategies for Neuroblastoma","volume":"33","author":"Pinto","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Baldari, S., Di Modugno, F., Nistic\u00f2, P., and Toietta, G. (2022). Strategies for Efficient Targeting of Tumor Collagen for Cancer Therapy. Cancers, 14.","DOI":"10.3390\/cancers14194706"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/ng.3438","article-title":"TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors","volume":"47","author":"Valentijn","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrc3526","article-title":"Neuroblastoma: Developmental biology, cancer genomics and immunotherapy","volume":"13","author":"Cheung","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1086\/424530","article-title":"Germline PHOX2B Mutation in Hereditary Neuroblastoma","volume":"75","author":"Mosse","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1200\/JCO.2009.27.8861","article-title":"Antitumor Activity of Hu14.18-IL2 in Patients With Relapsed\/Refractory Neuroblastoma: A Children\u2019s Oncology Group (COG) Phase II Study","volume":"28","author":"Shusterman","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Yang, J., Zhou, J., Li, C., and Wang, S. (2021). Integrated analysis of the functions and prognostic values of RNA-binding proteins in neuroblastoma. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260876"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cels.2018.05.014","article-title":"MHCflurry: Open-Source Class I MHC Binding Affinity Prediction","volume":"7","author":"Rubinsteyn","year":"2018","journal-title":"Cell Syst."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"D436","DOI":"10.1093\/nar\/gkae1092","article-title":"The Immune Epitope Database (IEDB): 2024 update","volume":"53","author":"Vita","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s002510050595","article-title":"SYFPEITHI: Database for MHC ligands and peptide motifs","volume":"50","author":"Rammensee","year":"1999","journal-title":"Immunogenetics"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"A Doytchinova, I., and Flower, D.R. (2007). VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-4"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2014A server for in silico prediction of allergens","volume":"20","author":"Dimitrov","year":"2014","journal-title":"J. Mol. Model."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1093\/bioinformatics\/btp137","article-title":"The PickPocket method for predicting binding specificities for receptors based on receptor pocket similarities: Application to MHC-peptide binding","volume":"25","author":"Zhang","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.gendis.2021.12.020","article-title":"Single-cell landscape analysis reveals distinct regression trajectories and novel prognostic biomarkers in primary neuroblastoma","volume":"9","author":"Liu","year":"2022","journal-title":"Genes Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.4049\/jimmunol.1600808","article-title":"Unsupervised HLA Peptidome Deconvolution Improves Ligand Prediction Accuracy and Predicts Cooperative Effects in Peptide\u2013HLA Interactions","volume":"197","author":"Gfeller","year":"2016","journal-title":"J. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Wu, J., Wang, W., Zhang, J., Zhou, B., Zhao, W., Su, Z., Gu, X., Wu, J., Zhou, Z., and Chen, S. (2019). DeepHLApan: A Deep Learning Approach for Neoantigen Prediction Considering Both HLA-Peptide Binding and Immunogenicity. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02559"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1158\/2326-6066.CIR-19-0464","article-title":"High-Throughput Prediction of MHC Class I and II Neoantigens with MHCnuggets","volume":"8","author":"Shao","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-1-0716-0327-7_17","article-title":"EPIC: A Tool to Estimate the Proportions of Different Cell Types from Bulk Gene Expression Data","volume":"2120","author":"Racle","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Suri, S., and Dakshanamurthy, S. (2022). IntegralVac: A Machine Learning-Based Comprehensive Multivalent Epitope Vaccine Design Method. Vaccines, 10.","DOI":"10.3390\/vaccines10101678"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"238","DOI":"10.33545\/26649926.2025.v7.i6d.383","article-title":"An AI-enabled single-cell approach to analyze the cancer immune microenvironment","volume":"7","author":"Shrungare","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Davalos, O.A., Heydari, A.A., Fertig, E.J., Sindi, S.S., and Hoyer, K.K. (2023). Boosting single-cell RNA sequencing analysis with simple neural attention. bioRxiv.","DOI":"10.1101\/2023.05.29.542760"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.annonc.2020.05.008","article-title":"Neoantigen prediction and computational perspectives towards clinical benefit: Recommendations from the ESMO Precision Medicine Working Group","volume":"31","author":"Vazquez","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"102176","DOI":"10.1016\/j.tranon.2024.102176","article-title":"The triad in current neuroblastoma challenges: Targeting antigens, enhancing effective cytotoxicity and accurate 3D in vitro modelling","volume":"51","author":"King","year":"2025","journal-title":"Transl. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1079\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:01:55Z","timestamp":1774533715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":108,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cancers18071079"],"URL":"https:\/\/doi.org\/10.3390\/cancers18071079","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]}}}