{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:02:42Z","timestamp":1787241762851,"version":"build-2736575974"},"reference-count":27,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T00:00:00Z","timestamp":1452211200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.<\/ns4:p>","DOI":"10.12688\/f1000research.7599.1","type":"journal-article","created":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T05:10:06Z","timestamp":1452229806000},"page":"38","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Rituximab efficiently depletes B cells in lung tumors\u00a0and normal lung tissue"],"prefix":"10.12688","volume":"5","author":[{"given":"Albane","family":"Joly-Battaglini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislava","family":"Stankovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Aamodt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Stj\u00e4rne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odd Terje","family":"Brustugun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5slaug","family":"Helland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"\u00d8ynebr\u00e5ten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Corthay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2016,1,8]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1519-1524","DOI":"10.4049\/jimmunol.1490027","article-title":"Translational medicine in action: anti-CD20 therapy in lymphoma.","volume":"193","author":"S Lim","year":"2014","journal-title":"J Immunol."},{"key":"ref-2","doi-asserted-by":"crossref","first-page":"435-445","DOI":"10.1182\/blood.V83.2.435.435","article-title":"Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20.","volume":"83","author":"M Reff","year":"1994","journal-title":"Blood."},{"key":"ref-3","doi-asserted-by":"crossref","first-page":"2457-2466","DOI":"10.1182\/blood.V84.8.2457.2457","article-title":"Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma.","volume":"84","author":"D Maloney","year":"1994","journal-title":"Blood."},{"key":"ref-4","doi-asserted-by":"crossref","first-page":"2188-2195","DOI":"10.1182\/blood.V90.6.2188","article-title":"IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma.","volume":"90","author":"D Maloney","year":"1997","journal-title":"Blood."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"2572-2581","DOI":"10.1056\/NEJMoa032534","article-title":"Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.","volume":"350","author":"J Edwards","year":"2004","journal-title":"N Engl J Med."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"676-688","DOI":"10.1056\/NEJMoa0706383","article-title":"B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.","volume":"358","author":"S Hauser","year":"2008","journal-title":"N Engl J Med."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"221-232","DOI":"10.1056\/NEJMoa0909905","article-title":"Rituximab versus cyclophosphamide for ANCA-associated vasculitis.","volume":"363","author":"J Stone","year":"2010","journal-title":"N Engl J Med."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"3251-3256","DOI":"10.1002\/art.24903","article-title":"Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sj\u00f6gren's syndrome.","volume":"60","author":"J Pijpe","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"271-280","DOI":"10.1093\/rheumatology\/kep093","article-title":"Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study.","volume":"49","author":"D Daoussis","year":"2010","journal-title":"Rheumatology (Oxford)."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"3940-3947","DOI":"10.1200\/JCO.2003.05.013","article-title":"Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma.","volume":"21","author":"W Weng","year":"2003","journal-title":"J Clin Oncol."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"455-459","DOI":"10.1002\/art.10764","article-title":"The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus.","volume":"48","author":"J Anolik","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"3909-3918","DOI":"10.1002\/art.22967","article-title":"Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment.","volume":"56","author":"Y Teng","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"604-612","DOI":"10.1309\/UXLE9RHL968TER7B","article-title":"Rituximab-induced changes in hematolymphoid tissues found at autopsy.","volume":"130","author":"A Cioc","year":"2008","journal-title":"Am J Clin Pathol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"4394-4400","DOI":"10.1182\/blood-2011-03-344051","article-title":"Immunologic effects of rituximab on the human spleen in immune thrombocytopenia.","volume":"118","author":"S Audia","year":"2011","journal-title":"Blood."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"e0129898","DOI":"10.1371\/journal.pone.0129898","article-title":"B-Lymphocyte Depletion in Myalgic Encephalopathy\/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment.","volume":"10","author":"Fluge","year":"2015","journal-title":"PLoS One."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"63-70","DOI":"10.1016\/j.jneuroim.2006.06.029","article-title":"Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients.","volume":"180","author":"A Cross","year":"2006","journal-title":"J Neuroimmunol."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"707-714","DOI":"10.1001\/archneurol.2010.99","article-title":"Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis.","volume":"67","author":"L Piccio","year":"2010","journal-title":"Arch Neurol."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"1464-1477","DOI":"10.1002\/art.22603","article-title":"BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sj\u00f6gren's syndrome.","volume":"56","author":"J Pers","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"772-778","DOI":"10.1002\/art.22400","article-title":"Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis.","volume":"56","author":"K Vos","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"402-408","DOI":"10.1136\/ard.2007.074229","article-title":"Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results.","volume":"67","author":"A Kavanaugh","year":"2008","journal-title":"Ann Rheum Dis."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"581-587","DOI":"10.1016\/j.rmed.2012.01.001","article-title":"Rituximab therapy for refractory interstitial lung disease related to antisynthetase syndrome.","volume":"106","author":"I Marie","year":"2012","journal-title":"Respir Med."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"e229","DOI":"10.1097\/MD.0000000000000229","article-title":"Prolonged B cell depletion with rituximab is effective in treating refractory pulmonary granulomatous inflammation in granulomatosis with polyangiitis (GPA).","volume":"93","author":"S Henderson","year":"2014","journal-title":"Medicine (Baltimore)."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"653-662","DOI":"10.1093\/rheumatology\/ker290","article-title":"Non-infectious pulmonary toxicity of rituximab: a systematic review.","volume":"51","author":"A Hadjinicolaou","year":"2012","journal-title":"Rheumatol (Oxford)."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"922-934","DOI":"10.1002\/ppul.20864","article-title":"Rituximab (B-cell depleting antibody) associated lung injury (RALI): a pediatric case and systematic review of the literature.","volume":"44","author":"M Bitzan","year":"2009","journal-title":"Pediatr Pulmonol."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"832-844","DOI":"10.1164\/rccm.201309-1611OC","article-title":"Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer.","volume":"189","author":"C Germain","year":"2014","journal-title":"Am J Respir Crit Care Med."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"1146-1155","DOI":"10.4161\/onci.21542","article-title":"A model for cancer-suppressive inflammation.","volume":"1","author":"O Haabeth","year":"2012","journal-title":"Oncoimmunology."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3389\/fimmu.2014.00197","article-title":"Does the immune system naturally protect against cancer?","volume":"5","author":"A Corthay","year":"2014","journal-title":"Front Immunol."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/5-38\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/5-38\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/5-38\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T14:58:10Z","timestamp":1600009090000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/5-38\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,8]]},"references-count":27,"URL":"https:\/\/doi.org\/10.12688\/f1000research.7599.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.8182.r12922","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.8182.r12242","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.8182.r12242","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.8182.r12922","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,8]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/5-38\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.8182.r12242, Bertrand Huard, Department of Oncogenesis and Biotechnology, Joseph Fourier University, Grenoble, France, 03 Feb 2016, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/5-38\/v1#referee-response-12242","order":0,"name":"referee-response-12242","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.8182.r12922, Hilde Schjerven, Etapong Fonabei Ayongaba, Department of Laboratory Medicine, School of Medicine, University of California, San Francisco, San Francisco, CA, USA, 29 Mar 2016, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/5-38\/v1#referee-response-12922","order":1,"name":"referee-response-12922","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Alexandre Corthay<\/b>; <i>Posted: 25 Feb 2016<\/i>; Thank you very much for your comment and for making us aware of the RRID initiative which we support. RRIDs will be included in the next version of our paper.","URL":"https:\/\/f1000research.com\/articles\/5-38\/v1#article-response-1835","order":2,"name":"article-response-1835","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"<b>Anita Bandrowski<\/b>; <i>Posted: 23 Feb 2016<\/i>; In testing a new tool for methods review, I detected the following research resources in your paper which did not contain the RRID ( <u>R<\/u>esearch <u>R<\/u>esource <u>ID<\/u>entifier). As discussed in the instructions to authors, please consider adding these to the final version of your paper.RRIDs are universal and persistent product codes and are used for antibodies, software tools and model organisms, see instructions to authors:&nbsp;http:\/\/f1000research.com\/for-authors\/article-guidelines\/research-notesPlease verify the accuracy of the RRIDs below: <i><b>Needs attention, not an exact match:Lab Vision Cat# RM-9107-R7, RRID:AB_149921 &nbsp;&nbsp;&nbsp; &nbsp;verify:&nbsp;<\/b><\/i>scicrunch.org\/resolver\/RRID:AB_149921&nbsp; <i><b>&nbsp;&nbsp; &nbsp;or search:&nbsp;<\/b><\/i>scicrunch.org\/resources\/Any\/search?q=RM-9107 <b>Exact match based on catalog number detected:<\/b>BioLegend Cat# 307610, RRID:AB_314688&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_314688BioLegend Cat# 304029, RRID:AB_2174123&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_2174123BioLegend Cat# 302227, RRID:AB_893276&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_893276BioLegend Cat# 325617, RRID:AB_830690&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_830690BioLegend Cat# 344713, RRID:AB_2044005&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_2044005BioLegend Cat# 317409, RRID:AB_571954&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_571954&nbsp;BioLegend Cat# 300415, RRID:AB_389310&nbsp;&nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_389310Dako Cat# M0755, RRID:AB_2282030 &nbsp; <b>verify<\/b>:&nbsp;scicrunch.org\/resolver\/RRID:AB_2282030Please consider verifying each antibody highlighted above against the identifier and adding the syntax (vendor catalog RRID) to the final version of the paper.","URL":"https:\/\/f1000research.com\/articles\/5-38\/v1#article-response-1828","order":3,"name":"article-response-1828","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"This work was supported by grants from the Research Council of Norway, Norway Grants 2009-2014 under project contract NFI\/R\/2014\/051 (to A. Corthay), and the Norwegian Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}