{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:26:42Z","timestamp":1783056402743,"version":"3.54.6"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have demonstrated promising therapeutic potential in head and neck squamous cell carcinoma (HNSCC). However, their clinical efficacy remains limited due to low response rates, largely attributed to the highly immunosuppressive tumor microenvironment (TME). Neutrophil extracellular traps (NETs) have recently been implicated in tumor progression and immune regulation. Therefore, this study aims to investigate the role of NETs in the TME and metastasis of HNSCC, and then to utilize cationic nanoparticles (cNP) to efficiently disrupt NETs in order to improve the immunosuppressive TME and inhibit metastasis, thereby suppressing the progression of HNSCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Histological and bioinformatics analyses were performed to evaluate NET-related signatures in HNSCC tissues and their association with immune cell infiltration.\n                      <jats:italic>In vitro<\/jats:italic>\n                      (scratch, cell adhesion and cytoskeletal remodeling assay) and\n                      <jats:italic>in vivo<\/jats:italic>\n                      (flow cytometry, immunofluorescence staining) experiments were conducted to investigate the effects of cationic nanoparticles (cNP) on NETs disruption, tumor cell migration, therapeutic efficacy and modulation of the TME. The underlying mechanism by which NET-DNA promotes HNSCC cell migration via CCDC25 was assessed using multiple approaches. Specifically, histological and immunohistochemical staining, western blotting, transfection, qRT-PCR, and transwell assays were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histological analysis revealed that the expression level of NETs in HNSCC tissue was significantly higher than that in adjacent normal tissue. Bioinformatics analysis revealed that high expression of myeloperoxidase (MPO) gene is closely related to immunosuppressive cell infiltration. Further analysis revealed that arm-level gain of the MPO gene was significantly correlated with a decrease in the infiltration levels of various immune cells.\n                      <jats:italic>In vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments demonstrated that cNP effectively disrupted NETs, inhibited tumor cell migration, and reversed the immunosuppressive TME. Compared with anti-PD-1 monotherapy, cNP combined with anti-PD-1 therapy synergistically inhibited tumor growth, prolonged survival, and significantly increased the proportion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and CD19\n                      <jats:sup>+<\/jats:sup>\n                      B cells, while simultaneously inhibiting the infiltration levels of Treg cells and M-MDSCs, and promoting macrophage polarization from M2 to M1 types, significantly alleviating the immunosuppressive state of TME. Immunofluorescence staining further confirmed that cNP or cNP combined with anti-PD-1 therapy effectively reduced NET-DNA deposition in tumor tissue. Regarding migration mechanisms, NET-DNA can promote HNSCC cell migration through its receptor CCDC25.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study reveals the key role of NETs in immune escape and metastasis of HNSCC and confirms that cNP disrupting NETs can synergistically enhance the efficacy of anti-PD-1 therapy, providing a new combination therapy strategy for HNSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1803439","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:48:09Z","timestamp":1776836889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cationic nanoparticles with disrupting neutrophil extracellular traps inhibit the progression of head and neck squamous cell carcinoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhaoqiang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guichao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3389\/fimmu.2013.00048","article-title":"A proposed role for neutrophil extracellular traps in cancer immunoediting","volume":"4","author":"Berger-Achituv","year":"2013","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s40265-023-01835-2","article-title":"Treating head and neck cancer in the age of immunotherapy: a 2023 update","volume":"83","author":"Bhatia","year":"2023","journal-title":"Drugs"},{"key":"B3","doi-asserted-by":"publisher","first-page":"6995","DOI":"10.3390\/ijms22136995","article-title":"Macrophage polarization states in the tumor microenvironment","volume":"22","author":"Boutilier","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"12150","DOI":"10.1038\/ncomms12150","article-title":"Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards","volume":"7","author":"Bronte","year":"2016","journal-title":"Nat. Communications"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/s41467-023-36691-x","article-title":"Single-cell transcriptome profiling of the stepwise progression of head and neck cancer","volume":"14","author":"Choi","year":"2023","journal-title":"Nat. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40425-019-0662-5","article-title":"The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)","volume":"7","author":"Cohen","year":"2019","journal-title":"J. Immunotherapy Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e22946","DOI":"10.4161\/onci.22946","article-title":"Neutrophil extracellular traps: a new link to cancer-associated thrombosis and potential implications for tumor progression","volume":"2","author":"Demers","year":"2013","journal-title":"Oncoimmunology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3973","DOI":"10.2147\/CMAR.S277907","article-title":"Further understanding of the immune microenvironment in head and neck squamous cell carcinoma: implications for prognosis","volume":"13","author":"Denaro","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/nrc3611","article-title":"Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms","volume":"13","author":"Elinav","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1075260","DOI":"10.3389\/fimmu.2022.1075260","article-title":"No NETs no TIME: crosstalk between neutrophil extracellular traps and the tumor immune microenvironment","volume":"13","author":"Fang","year":"2022","journal-title":"Front. Immunology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.3892\/or.2018.6657","article-title":"Tumor associated macrophages induce epithelial to mesenchymal transition via the EGFR\/ERK1\/2 pathway in head and neck squamous cell carcinoma","volume":"40","author":"Gao","year":"2018","journal-title":"Oncol. Reports"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e37387","DOI":"10.1097\/MD.0000000000037387","article-title":"Advances in tumor immune microenvironment of head and neck squamous cell carcinoma: a review of literature","volume":"103","author":"Hong","year":"2024","journal-title":"Medicine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1490853","DOI":"10.1080\/2162402X.2018.1490853","article-title":"TGF-\u03b21 programmed myeloid-derived suppressor cells (MDSC) acquire immune-stimulating and tumor killing activity capable of rejecting established tumors in combination with radiotherapy","volume":"7","author":"Jayaraman","year":"2018","journal-title":"Oncoimmunology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.canlet.2019.10.013","article-title":"Communication between EMT and PD-L1 signaling: new insights into tumor immune evasion","volume":"468","author":"Jiang","year":"2020","journal-title":"Cancer Lett."},{"key":"B15","first-page":"10","article-title":"Role of the tumor microenvironment in PD-L1\/PD-1-mediated","volume-title":"Mol. Cancer","author":"Jiang","year":"2019"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.1038\/bjc.2013.645","article-title":"Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients","volume":"109","author":"Jie","year":"2013","journal-title":"Br. Journal Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.5858\/arpa.2014-0498-RA","article-title":"Mechanisms of invasion in head and neck cancer","volume":"139","author":"Jimenez","year":"2015","journal-title":"Archives Pathology and Laboratory Medicine"},{"key":"B18","doi-asserted-by":"publisher","first-page":"785222","DOI":"10.3389\/fimmu.2021.785222","article-title":"Neutrophil extracellular traps promote T cell exhaustion in the tumor microenvironment","volume":"12","author":"Kaltenmeier","year":"2021","journal-title":"Front. Immunology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.imbio.2014.07.017","article-title":"Myeloid regulatory cells in tumor spreading and metastasis","volume":"220","author":"Keskinov","year":"2015","journal-title":"Immunobiology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"240","DOI":"10.3390\/ijms22010240","article-title":"Current trends and future prospects of molecular targeted therapy in head and neck squamous cell carcinoma","volume":"22","author":"Kitamura","year":"2020","journal-title":"Int. Journal Molecular Sciences"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2868","DOI":"10.1021\/acsnano.2c11280","article-title":"Nanoparticulate cationic poly (amino acid) s block cancer metastases by destructing neutrophil extracellular traps","volume":"17","author":"Liang","year":"2023","journal-title":"ACS Nano"},{"key":"B22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"B23","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/s41392-020-00285-6","article-title":"CCDC25: precise navigator for neutrophil extracellular traps on the prometastatic road","volume":"5","author":"Liu","year":"2020","journal-title":"Signal Transduct. Target Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.bioactmat.2021.10.044","article-title":"The protein Corona modulates the inflammation inhibition by cationic nanoparticles via cell-free DNA scavenging","volume":"13","author":"Liu","year":"2022","journal-title":"Bioact. Mater."},{"key":"B25","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1158\/1078-0432.CCR-21-1816","article-title":"Tadalafil enhances immune signatures in response to neoadjuvant nivolumab in resectable head and neck squamous cell carcinoma","volume":"28","author":"Luginbuhl","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.3389\/fimmu.2020.01749","article-title":"The emerging role of neutrophil extracellular traps (NETs) in tumor progression and metastasis","volume":"11","author":"Masucci","year":"2020","journal-title":"Front. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.ccell.2020.07.002","article-title":"Neutrophil DNA webs untangled","volume":"38","author":"Milette","year":"2020","journal-title":"Cancer Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0295863","DOI":"10.1371\/journal.pone.0295863","article-title":"Deciphering the immune landscape of head and neck squamous cell carcinoma: a single-cell transcriptomic analysis of regulatory T cell responses to PD-1 blockade therapy","volume":"18","author":"Miraki Feriz","year":"2023","journal-title":"Plos One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jaut.2015.08.018","article-title":"The responses of macrophages in interaction with neutrophils that undergo NETosis","volume":"67","author":"Nakazawa","year":"2016","journal-title":"J. Autoimmun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1182\/blood-2016-06-722298","article-title":"In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps","volume":"129","author":"Noubouossie","year":"2017","journal-title":"Blood, J. Am. Soc. Hematol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e1341030","DOI":"10.1080\/2162402X.2017.1341030","article-title":"Clinical relevance of tumor infiltrating lymphocytes, PD-L1 expression and correlation with HPV\/p16 in head and neck cancer treated with bio-or chemo-radiotherapy","volume":"6","author":"Ou","year":"2017","journal-title":"Oncoimmunology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"361ra138","DOI":"10.1126\/scitranslmed.aag1711","article-title":"Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps","volume":"8","author":"Park","year":"2016","journal-title":"Sci. Translational Medicine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e23414","DOI":"10.1096\/fj.202301064RR","article-title":"Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-\u03baB signaling pathway","volume":"38","author":"Qian","year":"2024","journal-title":"Faseb J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","article-title":"Cytotoxic CD8+ T cells in cancer and cancer immunotherapy","volume":"124","author":"Raskov","year":"2021","journal-title":"Br. Journal Cancer"},{"key":"B37","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41389-022-00398-3","article-title":"Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy","volume":"11","author":"Raskov","year":"2022","journal-title":"Oncogenesis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1097\/TP.0000000000003180","article-title":"Exploring the relationship between circulating M-MDSC numbers and risk of posttransplant malignancy","volume":"104","author":"Riquelme","year":"2020","journal-title":"Transplantation"},{"key":"B39","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.ccell.2015.02.015","article-title":"Macrophages and therapeutic resistance in cancer","volume":"27","author":"Ruffell","year":"2015","journal-title":"Cancer Cell"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1007\/s00262-022-03313-2","article-title":"Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy","volume":"72","author":"Rutihinda","year":"2023","journal-title":"Cancer Immunol. Immunother."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-018-0620-1","article-title":"Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell carcinoma of the head and neck","volume":"18","author":"She","year":"2018","journal-title":"Cancer Cell International"},{"key":"B42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"Cancer Stat."},{"key":"B43","doi-asserted-by":"publisher","first-page":"722","DOI":"10.3109\/08820139.2012.678023","article-title":"Highlights on molecular mechanisms of MDSC-Mediated immune suppression: paving the way for new working hypotheses","volume":"41","author":"Solito","year":"2012","journal-title":"Immunol. Investigations"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1158\/0008-5472.CAN-23-2986","article-title":"DNA of neutrophil extracellular traps binds TMCO6 to impair CD8+ T-cell immunity in hepatocellular carcinoma","volume":"84","author":"Song","year":"2024","journal-title":"Cancer Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/s41577-020-00490-y","article-title":"Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity","volume":"21","author":"Veglia","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1093\/intimm\/dxg020","article-title":"Synergy between cpg\u2010or non\u2010cpg DNA and specific antigen for B cell activation","volume":"15","author":"Wang","year":"2003","journal-title":"Int. Immunology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.3389\/fonc.2019.01084","article-title":"Targeting the immune microenvironment in the treatment of head and neck squamous cell carcinoma","volume":"9","author":"Wang","year":"2019","journal-title":"Front. Oncol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.jhep.2021.07.032","article-title":"Regulatory T-cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis","volume":"75","author":"Wang","year":"2021","journal-title":"J. Hepatology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1126\/science.aaa8064","article-title":"Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis","volume":"349","author":"Warnatsch","year":"2015","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12943-019-0976-4","article-title":"Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis","volume":"18","author":"Wei","year":"2019","journal-title":"Mol. Cancer"},{"key":"B51","doi-asserted-by":"publisher","first-page":"574260","DOI":"10.3389\/fonc.2021.574260","article-title":"PLAU1 facilitated proliferation, invasion, and metastasis via interaction with MMP1 in head and neck squamous carcinoma","volume":"11","author":"Wu","year":"2021","journal-title":"Front. Oncol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13045-022-01242-2","article-title":"Improvement of the anticancer efficacy of PD-1\/PD-L1 blockade via combination therapy and PD-L1 regulation","volume":"15","author":"Wu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1135086","DOI":"10.3389\/fimmu.2023.1135086","article-title":"Neutrophil extracellular traps in tumor progression and immunotherapy","volume":"14","author":"Yan","year":"2023","journal-title":"Front. Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41586-020-2394-6","article-title":"DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25","volume":"583","author":"Yang","year":"2020","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","first-page":"8316525","DOI":"10.1155\/2022\/8316525","article-title":"Neutrophil extracellular traps facilitate A549 cell invasion and migration in a macrophage\u2010maintained inflammatory microenvironment","volume":"2022","author":"Zhang","year":"2022","journal-title":"BioMed Res. Int."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1053\/j.gastro.2016.02.040","article-title":"Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib","volume":"150","author":"Zhou","year":"2016","journal-title":"Gastroenterology"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1803439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:48:10Z","timestamp":1776836890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1803439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":56,"alternative-id":["10.3389\/fcell.2026.1803439"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1803439","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]},"article-number":"1803439"}}