{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:04:02Z","timestamp":1789009442734,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alfonso Mart\u00edn Escudero Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Bruton\u2019s tyrosine kinase inhibitor ibrutinib has significantly changed treatment landscape in chronic lymphocytic leukemia (CLL). Growing evidence supports ibrutinib to work beyond the effect on tumor cells by means of, for example, restoring functionality of the T-cell compartment and increasing circulating T-cell numbers. Recent evidence suggests T-cell enhanced expansion, rather than increased egress from secondary lymphoid organs (SLO), as a root cause for ibrutinib-induced lymphocytosis. However, whether the latter physiological change is also a consequence of a forced retention in blood remains undisclosed. Since CCR7 is the main chemokine receptor taking over the homing of T-cells from peripheral compartments to lymph nodes and other SLO, we aimed to investigate the impact of ibrutinib on CCR7 functionality in T-cells. To this end, we documented receptor expression in T-cells from a large cohort of ibrutinib-treated CLL patients, and performed different in vivo and in vitro migration models. Overall, our data confirm that CCR7 expression or receptor-mediated migration in CLL T-cells is not affected by ibrutinib. Furthermore, it does not modulate CCR7-driven homing nor nodal interstitial migration. Together, our results support that ibrutinib-induced CLL T-cell accumulation in the blood stream is not derived from an impairment of CCR7-driven recirculation between the SLO and bloodstream, and therefore T-cell expansion is the most plausible cause.<\/jats:p>","DOI":"10.3390\/cancers14112729","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T09:24:29Z","timestamp":1653989069000},"page":"2729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Tamara","family":"Mateu-Albero","sequence":"first","affiliation":[{"name":"Immunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7606-3580","authenticated-orcid":false,"given":"Ana","family":"Marcos-Jimenez","sequence":"additional","affiliation":[{"name":"Immunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, Spain"},{"name":"Department of Oncology, Microbiology and Immunology, University of Fribourg, CH-1700 Freiburg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Wissmann","sequence":"additional","affiliation":[{"name":"Department of Oncology, Microbiology and Immunology, University of Fribourg, CH-1700 Freiburg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Loscertales","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Terr\u00f3n","sequence":"additional","affiliation":[{"name":"IMMED S.L., Immunological and Medicinal Products, C\/Vel\u00e1zquez 57, 6\u00ba derecha, 28001 Madrid, Spain"},{"name":"Catapult Therapeutics, 8243 RC Lelystad, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8199-9586","authenticated-orcid":false,"given":"Jens V.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Oncology, Microbiology and Immunology, University of Fribourg, CH-1700 Freiburg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Mu\u00f1oz-Calleja","sequence":"additional","affiliation":[{"name":"Immunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, Spain"},{"name":"School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-9790","authenticated-orcid":false,"given":"Carlos","family":"Cuesta-Mateos","sequence":"additional","affiliation":[{"name":"Immunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, Spain"},{"name":"IMMED S.L., Immunological and Medicinal Products, C\/Vel\u00e1zquez 57, 6\u00ba derecha, 28001 Madrid, Spain"},{"name":"Catapult Therapeutics, 8243 RC Lelystad, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/bjh.15918","article-title":"Chronic lymphocytic leukaemia: The role of T cells in a B cell disease","volume":"186","author":"Man","year":"2019","journal-title":"Br. 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