{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:13:35Z","timestamp":1791825215635,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Bruton\u2019s tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCR\u03b2-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy. We noted elevated CD4+ and CD8+ T cell numbers and a restricted TCR\u03b2 repertoire in all pretreatment samples. After 1 y of ibrutinib therapy, elevated peripheral blood T cell numbers and T cell\u2013related cytokine levels had normalized, and T cell repertoire diversity increased significantly. Dominant TCR\u03b2 clones in pretreatment samples declined or became undetectable, and the number of productive unique clones increased significantly during ibrutinib therapy, with the emergence of large numbers of low-frequency TCR\u03b2 clones. Importantly, broader TCR repertoire diversity was associated with clinical efficacy and lower rates of infections during ibrutinib therapy. These data demonstrate that ibrutinib therapy increases diversification of the T cell compartment in CLL patients, which contributes to cellular immune reconstitution.<\/jats:p>","DOI":"10.4049\/jimmunol.1601190","type":"journal-article","created":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T02:10:51Z","timestamp":1484187051000},"page":"1740-1747","source":"Crossref","is-referenced-by-count":111,"title":["Ibrutinib Therapy Increases T Cell Repertoire Diversity in Patients with Chronic Lymphocytic Leukemia"],"prefix":"10.1093","volume":"198","author":[{"given":"Qingsong","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"},{"name":"Department of Leukemia, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Institute of Hematology , Zhengzhou, Henan 450009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Sivina","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan","family":"Robins","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies , Seattle, WA 98102"},{"name":"Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Yusko","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies , Seattle, WA 98102"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Vignali","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies , Seattle, WA 98102"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9121-6450","authenticated-orcid":false,"given":"Michael J","family":"Keating","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ferrajoli","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeev","family":"Estrov","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"Wierda","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77230"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,15]]},"reference":[{"key":"2025030615032747500_r1","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1056\/NEJMra041720","article-title":"Chronic lymphocytic leukemia","volume":"352","author":"Chiorazzi","year":"2005","journal-title":"N. 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