{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:50:40Z","timestamp":1791654640950,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300214"],"award-info":[{"award-number":["82300214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270195"],"award-info":[{"award-number":["82270195"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["Y\u2010NCJH202204\u20100002"],"award-info":[{"award-number":["Y\u2010NCJH202204\u20100002"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bispecific antibodies (BsAbs) targeting CD20 \u00d7 CD3 have achieved remarkable efficacy in relapsed or refractory (R\/R) B\u2010cell lymphoma, yet clinical responses remain heterogeneous and predictive biomarkers are lacking. We retrospectively evaluated associations between peripheral immune profiles and outcomes in 40 patients treated with CD20 \u00d7 CD3 BsAbs and explored BTK inhibitor\u2013associated immune changes using a paired BTK inhibitor cohort, functional assays, mouse models, and single\u2010cell RNA sequencing. Higher baseline CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell counts correlated with superior response rates and prolonged progression\u2010free survival, whereas CD8\n                    <jats:sup>+<\/jats:sup>\n                    counts showed no association. Elevated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell levels were linked to increased activation of effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    T cells and greater induction of IL\u20102 and IFN\u2010\u03b3 following treatment. Across paired clinical samples and experimental models, BTK inhibition was associated with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell expansion and enhanced T\/NK\u2010cell proliferative and cytotoxic signatures. In an exploratory real\u2010world observation, three patients received BTK inhibition before glofitamab; all achieved complete responses, with two remaining in remission at data cutoff and one relapsing after 8.4\u00a0months. These findings identify peripheral CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell reserve as a potential biomarker associated with BsAb outcomes and provide a rationale for further investigation of BTK inhibitor\u2013mediated immune modulation in BsAb treatment strategies.\n                  <\/jats:p>","DOI":"10.1002\/hon.70266","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:35:21Z","timestamp":1791653721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral CD4\n                    <sup>+<\/sup>\n                    T\u2010Cell Reserve as a Potential Biomarker of CD20 \u00d7 CD3 Bispecific Antibody Outcomes and BTK Inhibitor\u2013Associated Immune Modulation in B\u2010Cell Lymphoma"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-4832","authenticated-orcid":false,"given":"Hui","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0109-3869","authenticated-orcid":false,"given":"Jin","family":"Chai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaowu","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Department of Medical Oncology Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7659-1431","authenticated-orcid":false,"given":"Dingyao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Health Care Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0051-8112","authenticated-orcid":false,"given":"Zhao","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxiang","family":"Li","sequence":"additional","affiliation":[{"name":"King's College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2727-0289","authenticated-orcid":false,"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7678-3897","authenticated-orcid":false,"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3479-2547","authenticated-orcid":false,"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3067-5554","authenticated-orcid":false,"given":"Yuqin","family":"Song","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201003\u2010769620"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010023\u201000970\u2010z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011994"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(23)00521\u20104"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010024\u201000989\u2010w"},{"key":"e_1_2_10_7_1","article-title":"Outcomes of Bispecific Antibodies After CAR T\u2010Cell Failure for Large B\u2010Cell Lymphoma\u2010 Results From the ABC Consortium","author":"Melody M.","year":"2025","journal-title":"Blood Advances"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014903"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025029117"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2206913"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025772"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2024000677"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010840"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.962552"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102024\u2010199330"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102013\u201006\u2010507947"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci89756"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009517"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3056"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/30996"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2023.23.e41"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.09.003"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2024.285343"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100010\u20101"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci85309"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22079"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010025\u201006770\u20102"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020554"}],"container-title":["Hematological Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.70266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hon.70266","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.70266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:35:22Z","timestamp":1791653722000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hon.70266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/hon.70266"],"URL":"https:\/\/doi.org\/10.1002\/hon.70266","archive":["Portico"],"relation":{},"ISSN":["0278-0232","1099-1069"],"issn-type":[{"value":"0278-0232","type":"print"},{"value":"1099-1069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]},"assertion":[{"value":"2026-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70266"}}