{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:29:20Z","timestamp":1793996960329,"version":"4.8.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>NK cells can mediate tumor cell killing by natural cytotoxicity and by antibody-dependent cell-mediated cytotoxicity (ADCC), an anti-tumor mechanism mediated through the IgG Fc receptor CD16A (Fc\u03b3RIIIA). CD16A polymorphisms conferring increased affinity for IgG positively correlate with clinical outcomes during monoclonal antibody therapy for lymphoma, linking increased binding affinity with increased therapeutic potential via ADCC. We have previously reported on the Fc\u03b3R fusion CD64\/16A consisting of the extracellular region of CD64 (Fc\u03b3RI), a high-affinity Fc receptor normally expressed by myeloid cells, and the transmembrane\/cytoplasmic regions of CD16A, to create a highly potent and novel activating fusion receptor. Here, we evaluate the therapeutic potential of engineered induced pluripotent stem cell (iPSC)-derived NK (iNK) cells expressing CD64\/16A as an \u201coff-the-shelf\u201d, antibody-armed cellular therapy product with multi-antigen targeting potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>iNK cells were generated from iPSCs engineered to express CD64\/16A and an interleukin (IL)-15\/IL-15R\u03b1 fusion (IL-15RF) protein for cytokine independence. iNK cells and peripheral blood NK cells were expanded using irradiated K562-mbIL21\u201341BBL feeder cells to examine in <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> assays using the Raji lymphoma cell line. ADCC was evaluated in real-time by IncuCyte assays and using a xenograft mouse model with high circulating levels of human IgG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data show that CD64\/16A expressing iNK cells can mediate potent anti-tumor activity against human B cell lymphoma. In particular, (i) under suboptimal conditions, including low antibody concentrations and low effector-to-target ratios, iNK-CD64\/16A cells mediate ADCC, (ii) iNK-CD64\/16A cells can be pre-loaded with tumor-targeting antibodies (arming) to elicit ADCC, (iii) armed iNK-CD64\/16A cells can be repurposed with additional antibodies to target new tumor antigens, and (iv) cryopreserved, armed iNK-CD64\/16A are capable of sustained ADCC in a tumor xenograft model under saturating levels of human IgG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>iNK-CD64\/16A cells allow for a flexible use of antibodies (antibody arming and antibody targeting), and an \u201coff-the-shelf\u201d platform for multi-antigen recognition to overcome limitations of adoptive cell therapies expressing fixed antigen receptors leading to cancer relapse due to antigen escape variants.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1407567","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T04:30:26Z","timestamp":1721363426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["iPSC-derived NK cells expressing high-affinity IgG Fc receptor fusion CD64\/16A to mediate flexible, multi-tumor antigen targeting for lymphoma"],"prefix":"10.3389","volume":"15","author":[{"given":"Kate J.","family":"Dixon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Khaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hullsiek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary B.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders W.","family":"Matson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila","family":"Shirinbak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Hancock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Bjordahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hosking","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahram","family":"Valamehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Walcheck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00754-1","article-title":"Long-term outcomes following CAR T cell therapy: what we know so far","volume":"20","author":"Cappell","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph191912366","article-title":"Price and prejudice? The value of chimeric antigen receptor (CAR) T-cell therapy","volume":"19","author":"Choi","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djy193","article-title":"Cost-effectiveness of chimeric antigen receptor T-cell therapy in pediatric relapsed\/refractory B-cell acute lymphoblastic leukemia","volume":"111","author":"Sarkar","year":"2019","journal-title":"J Natl Cancer Inst"},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0184-6","article-title":"Mechanisms of resistance to CAR T cell therapy","volume":"16","author":"Shah","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222","article-title":"Chimeric antigen receptor T cells for sustained remissions in leukemia","volume":"371","author":"Maude","year":"2014","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61403-3","article-title":"T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial","volume":"385","author":"Lee","year":"2015","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.3011","article-title":"Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed\/refractory ALL","volume":"34","author":"Maude","year":"2016","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-08-665547","article-title":"Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy","volume":"127","author":"Gardner","year":"2016","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01281-7","article-title":"Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia","volume":"35","author":"Dourthe","year":"2021","journal-title":"Leukemia"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708566","article-title":"Chimeric antigen receptor T cells in refractory B-cell lymphomas","volume":"377","author":"Schuster","year":"2017","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021010930","article-title":"CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel","volume":"138","author":"Plaks","year":"2021","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01869","article-title":"Natural killer cells: development, maturation, and clinical utilization","volume":"9","author":"Abel","year":"2018","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.896228","article-title":"All about (NK cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity","volume":"13","author":"Ramirez-Labrada","year":"2022","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"103261","DOI":"10.1016\/j.critrevonc.2021.103261","article-title":"Natural Killer cells and monoclonal antibodies: Two partners for successful antibody dependent cytotoxicity against tumor cells","volume":"160","author":"Gauthier","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41577-022-00732-1","article-title":"Roles of natural killer cells in immunity to cancer, and applications to immunotherapy","volume":"23","author":"Wolf","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.2MR1218-501R","article-title":"Role of ADAM17 as a regulatory checkpoint of CD16A in NK cells and as a potential target for cancer immunotherapy","volume":"105","author":"Wu","year":"2019","journal-title":"J Leukoc Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167076","article-title":"Functional tissue analysis reveals successful cryopreservation of human osteoarthritic synovium","volume":"11","author":"Broeren","year":"2016","journal-title":"PloS One"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.522","article-title":"The unfolded protein response controls induction and activation of ADAM17\/TACE by severe hypoxia and ER stress","volume":"31","author":"Rzymski","year":"2012","journal-title":"Oncogene"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-425397","article-title":"NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17)","volume":"121","author":"Romee","year":"2013","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201712085","article-title":"Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells","volume":"217","author":"Srpan","year":"2018","journal-title":"J Cell Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.02.028","article-title":"IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer","volume":"145","author":"Felices","year":"2017","journal-title":"Gynecol Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7150\/jca.2.443","article-title":"Tumor induced inactivation of natural killer cell cytotoxic function; implication in growth, expansion and differentiation of cancer stem cells","volume":"2","author":"Jewett","year":"2011","journal-title":"J Cancer"},{"key":"B27","article-title":"Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma","volume":"2","author":"Lai","year":"1996","journal-title":"Clin Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-179754","article-title":"Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses","volume":"113","author":"Bruhns","year":"2009","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.3.754","article-title":"Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene","volume":"99","author":"Cartron","year":"2002","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02873","article-title":"Expression of a recombinant high affinity igG fc receptor by engineered NK cells as a docking platform for therapeutic mAbs to target cancer cells","volume":"9","author":"Snyder","year":"2018","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2019.1667974","article-title":"iNK-CD64\/16A cells: a promising approach for ADCC","volume":"19","author":"Walcheck","year":"2019","journal-title":"Expert Opin Biol Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007280","article-title":"iPSC-derived natural killer cells expressing the FcgammaR fusion CD64\/16A can be armed with antibodies for multitumor antigen targeting","volume":"11","author":"Snyder","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.01.014","article-title":"Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells","volume":"2","author":"Valamehr","year":"2014","journal-title":"Stem Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021015184","article-title":"Dual antigen-targeted off-the-shelf NK cells show durable response and prevent antigen escape in lymphoma and leukemia","volume":"140","author":"Cichocki","year":"2022","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz5618","article-title":"iPSC-derived NK cells maintain high cytotoxicity and enhance in vivo tumor control in concert with T cells and anti-PD-1 therapy","volume":"12","author":"Cichocki","year":"2020","journal-title":"Sci Transl Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1182\/blood.2019000621","article-title":"Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity","volume":"135","author":"Zhu","year":"2020","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01851","article-title":"A flow cytometry-based whole blood natural killer cell cytotoxicity assay using overnight cytokine activation","volume":"11","author":"Kim","year":"2020","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1016\/j.stem.2021.08.013","article-title":"Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy","volume":"28","author":"Woan","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5640","article-title":"Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity","volume":"96","author":"Mandelboim","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000326","article-title":"Serial killing of tumor cells by human natural killer cells\u2013enhancement by therapeutic antibodies","volume":"2","author":"Bhat","year":"2007","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00119","article-title":"Microchip screening platform for single cell assessment of NK cell cytotoxicity","volume":"7","author":"Guldevall","year":"2016","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nri2381","article-title":"Formation and function of the lytic NK-cell immunological synapse","volume":"8","author":"Orange","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2016.1218586","article-title":"The immunoglobulin G1 N-glycan composition affects binding to each low affinity Fc gamma receptor","volume":"8","author":"Subedi","year":"2016","journal-title":"MAbs"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0178","article-title":"Simultaneous engagement of tumor and stroma targeting antibodies by engineered NK-92 cells expressing CD64 controls prostate cancer growth","volume":"9","author":"Hintz","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.jim.2004.08.008","article-title":"CD107a as a functional marker for the identification of natural killer cell activity","volume":"294","author":"Alter","year":"2004","journal-title":"J Immunol Methods"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02664","article-title":"Mechanisms of relapse after CD19 CAR T-cell therapy for acute lymphoblastic leukemia and its prevention and treatment strategies","volume":"10","author":"Xu","year":"2019","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/antib9030034","article-title":"Monoclonal antibodies in cancer therapy","volume":"9","author":"Zahavi","year":"2020","journal-title":"Antibodies (Basel)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0414","article-title":"Fc-gamma receptor polymorphisms, cetuximab therapy, and survival in the NCIC CTG CO","volume":"22","author":"Liu","year":"2016","journal-title":"17 Trial Colorectal Cancer Clin Cancer Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119616","article-title":"A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease","volume":"100","author":"Wu","year":"1997","journal-title":"J Clin Invest"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-070656","article-title":"Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the FcgammaRIIIa-158 V\/V and V\/F polymorphism","volume":"110","author":"Hatjiharissi","year":"2007","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.51","article-title":"Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer","volume":"16","author":"Musolino","year":"2016","journal-title":"Pharmacogenomics J"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020312","article-title":"Engineering anti-tumor monoclonal antibodies and fc receptors to enhance ADCC by human NK cells","volume":"13","author":"Dixon","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.641521","article-title":"Antibody afucosylation augments CD16-mediated serial killing and IFN\u03b3 Secretion by human natural killer cells","volume":"12","author":"Karampatzakis","year":"2021","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jim.2005.07.025","article-title":"Fucose removal from complex-type oligosaccharide enhances the antibody-dependent cellular cytotoxicity of single-gene-encoded antibody comprising a single-chain antibody linked the antibody constant region","volume":"306","author":"Natsume","year":"2005","journal-title":"J Immunol Methods"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2263","article-title":"Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density","volume":"11","author":"Niwa","year":"2005","journal-title":"Clin Cancer Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202069200","article-title":"Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity","volume":"277","author":"Shields","year":"2002","journal-title":"J Biol Chem"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8378","article-title":"Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity","volume":"371","author":"Larsen","year":"2021","journal-title":"Science"},{"key":"B58","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/1471-2407-9-58","article-title":"Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood","volume":"9","author":"Iida","year":"2009","journal-title":"BMC Cancer"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210665200","article-title":"The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity","volume":"278","author":"Shinkawa","year":"2003","journal-title":"J Biol Chem"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1407567\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T04:30:29Z","timestamp":1721363429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1407567\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":59,"alternative-id":["10.3389\/fimmu.2024.1407567"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1407567","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,19]]},"article-number":"1407567"}}