{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:42:46Z","timestamp":1787503366609,"version":"build-2736575974"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Diffuse large B cell lymphomas (DLBCL) are a highly heterogeneous subtype of Non Hodgkin Lymphoma (NHL), accounting for about 25% of NHL. Despite an increased progression-free survival upon therapy, 40\u201350% of patients develop relapse\/refractory disease, therefore there remains an important medical need. T cell recruiting therapies, such as the CD20xCD3 T cell bi-specific antibody CD20-TCB (RG6026 or glofitamab), represent a novel approach to target all stages of DLBCL, especially those that fail to respond to multiple lines of treatment. We aimed for a better understanding of the molecular features related to the mode of action (MoA) of CD20-TCB in inducing Target\/T cell synapse formation and human T cell recruitment to the tumor. To directly evaluate the correlation between synapse, cytokine production and anti-tumor efficacy using CD20-TCB, we developed an innovative preclinical human DLBCL\n                    <jats:italic>in vivo<\/jats:italic>\n                    model that allowed tracking\n                    <jats:italic>in vivo<\/jats:italic>\n                    human T cell dynamics by multiphoton intravital microscopy (MP-IVM). By\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    approaches, we revealed that CD20-TCB is inducing strong and stable synapses between human T cell and tumor cells, which are dependent on the dose of CD20-TCB and on LFA-1 activity but not on FAS-L. Moreover, despite CD20-TCB being a large molecule (194.342 kDa), we observed that intra-tumor CD20-TCB-mediated human T cell-tumor cell synapses occur within 1 hour upon CD20-TCB administration. These tight interactions, observed for at least 72 hours post TCB administration, result in tumor cell cytotoxicity, resident T cell proliferation and peripheral blood T cell recruitment into tumor. By blocking the IFN\u03b3-CXCL10 axis, the recruitment of peripheral T cells was abrogated, partially affecting the efficacy of CD20-TCB treatment which rely only on resident T cell proliferation. Altogether these data reveal that CD20-TCB\u2019s anti-tumor activity relies on a triple effect: i) fast formation of stable T cell-tumor cell synapses which induce tumor cytotoxicity and cytokine production, ii) resident T cell proliferation and iii) recruitment of fresh peripheral T cells to the tumor core to allow a positive enhancement of the anti-tumor effect.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0241091","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T14:55:47Z","timestamp":1609944947000},"page":"e0241091","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cross-linking of T cell to B cell lymphoma by the T cell bispecific antibody CD20-TCB induces IFN\u03b3\/CXCL10-dependent peripheral T cell recruitment in humanized murine model"],"prefix":"10.1371","volume":"16","author":[{"given":"Floriana","family":"Cremasco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Menietti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Speziale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Sam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Sammicheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Richard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Varol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Umana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Bacac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Colombetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1375-8155","authenticated-orcid":true,"given":"Mario","family":"Perro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"pone.0241091.ref001","unstructured":"Noone AMHN, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, et al. 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Sci"},{"issue":"4","key":"pone.0241091.ref024","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s10585-008-9234-7","article-title":"Intravital microscopy of tumor angiogenesis and regression in the dorsal skin fold chamber: mechanistic insights and preclinical testing of therapeutic strategies","volume":"26","author":"GE Koehl","year":"2009","journal-title":"Clin Exp Metastasis"},{"issue":"15","key":"pone.0241091.ref025","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1242\/jcs.186205","article-title":"The cytotoxic T lymphocyte immune synapse at a glance","volume":"129","author":"NM Dieckmann","year":"2016","journal-title":"J Cell Sci"},{"issue":"9","key":"pone.0241091.ref026","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1002\/eji.201040345","article-title":"Sustained LFA-1 cluster formation in the immune synapse requires the combined activities of L-plastin and calmodulin","volume":"40","author":"GH Wabnitz","year":"2010","journal-title":"Eur J Immunol"},{"key":"pone.0241091.ref027","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.3389\/fimmu.2018.01943","article-title":"Xenogeneic Graft-Versus-Host Disease in Humanized NSG and NSG-HLA-A2\/HHD Mice","volume":"9","author":"G Ehx","year":"2018","journal-title":"Front Immunol"},{"issue":"2","key":"pone.0241091.ref028","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nri2017","article-title":"Humanized mice in translational biomedical research","volume":"7","author":"LD Shultz","year":"2007","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"pone.0241091.ref029","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nri.2017.49","article-title":"Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy","volume":"17","author":"N Nagarsheth","year":"2017","journal-title":"Nat Rev Immunol"},{"issue":"3681","key":"pone.0241091.ref030","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1126\/science.149.3681.310","article-title":"Interferon-Like Virus-Inhibitor Induced in Human Leukocytes by Phytohemagglutinin","volume":"149","author":"EF Wheelock","year":"1965","journal-title":"Science"},{"issue":"3886","key":"pone.0241091.ref031","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1126\/science.164.3886.1415","article-title":"Immune specific induction of interferon production in cultures of human blood lymphocytes","volume":"164","author":"JA Green","year":"1969","journal-title":"Science"},{"issue":"6","key":"pone.0241091.ref032","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1002\/1521-4141(200206)32:6<1792::AID-IMMU1792>3.0.CO;2-0","article-title":"Induction of the chemokine receptor CXCR3 on TCR-stimulated T cells: dependence on the release from persistent TCR-triggering and requirement for IFN-gamma stimulation","volume":"32","author":"C Nakajima","year":"2002","journal-title":"Eur J Immunol"},{"issue":"5","key":"pone.0241091.ref033","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/bjc.2016.172","article-title":"CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer","volume":"115","author":"H Bronger","year":"2016","journal-title":"Br J Cancer"},{"issue":"4","key":"pone.0241091.ref034","doi-asserted-by":"crossref","first-page":"583","DOI":"10.3892\/ol.2011.300","article-title":"The emerging role of CXCL10 in cancer (Review)","volume":"2","author":"M Liu","year":"2011","journal-title":"Oncol Lett"},{"issue":"3","key":"pone.0241091.ref035","doi-asserted-by":"crossref","first-page":"585","DOI":"10.4049\/jimmunol.1900496","article-title":"T Cell-Activating Bispecific Antibodies in Cancer Therapy","volume":"203","author":"A Trabolsi","year":"2019","journal-title":"J 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Wurzer","year":"2019","journal-title":"Cells"},{"issue":"3","key":"pone.0241091.ref041","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.4049\/jimmunol.179.3.1616","article-title":"LFA-1-mediated T cell costimulation through increased localization of TCR\/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse","volume":"179","author":"B Graf","year":"2007","journal-title":"J Immunol"},{"issue":"6","key":"pone.0241091.ref042","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.imbio.2008.11.014","article-title":"Mode of cytotoxic action of T cell-engaging BiTE antibody MT110","volume":"214","author":"C Haas","year":"2009","journal-title":"Immunobiology"},{"issue":"6","key":"pone.0241091.ref043","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1182\/blood.V95.6.2098","article-title":"A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes","volume":"95","author":"A Loffler","year":"2000","journal-title":"Blood"},{"issue":"11","key":"pone.0241091.ref044","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1158\/2326-6066.CIR-14-0161","article-title":"The immunological synapse","volume":"2","author":"ML Dustin","year":"2014","journal-title":"Cancer Immunol Res"},{"issue":"6","key":"pone.0241091.ref045","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1084\/jem.20112741","article-title":"Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2","volume":"209","author":"T Yokosuka","year":"2012","journal-title":"J Exp Med"},{"issue":"3","key":"pone.0241091.ref046","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2004.06.017","article-title":"B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse","volume":"21","author":"T Pentcheva-Hoang","year":"2004","journal-title":"Immunity"},{"key":"pone.0241091.ref047","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3389\/fimmu.2017.00309","article-title":"In Vivo Imaging Sheds Light on Immune Cell Migration and Function in Cancer","volume":"8","author":"T Torcellan","year":"2017","journal-title":"Front Immunol"},{"issue":"24","key":"pone.0241091.ref048","doi-asserted-by":"crossref","first-page":"6447","DOI":"10.1158\/1078-0432.CCR-18-1139","article-title":"IFNgamma-induced Chemokines Are Required for CXCR3-mediated T-Cell Recruitment and Antitumor Efficacy of Anti-HER2\/CD3 Bispecific Antibody","volume":"24","author":"J Li","year":"2018","journal-title":"Clin Cancer Res"},{"key":"pone.0241091.ref049","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T cells: mechanisms of differentiation and function","volume":"30","author":"SZ Josefowicz","year":"2012","journal-title":"Annu Rev 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checkpoints","volume":"6","author":"ME Mikucki","year":"2015","journal-title":"Nat Commun"},{"issue":"6382","key":"pone.0241091.ref054","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"CH June","year":"2018","journal-title":"Science"},{"key":"pone.0241091.ref055","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.3389\/fimmu.2017.01970","article-title":"Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands","volume":"8","author":"M Metzemaekers","year":"2017","journal-title":"Front Immunol"},{"key":"pone.0241091.ref056","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ctrv.2017.11.007","article-title":"CXCL9, CXCL10, CXCL11\/CXCR3 axis for immune activation\u2014A target for novel cancer therapy","volume":"63","author":"R 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