{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:49:22Z","timestamp":1791186562784,"version":"4.1.0"},"reference-count":62,"publisher":"American Association for Cancer Research (AACR)","issue":"12","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In human chronic lymphocytic leukemia (CLL) pathogenesis, B-cell antigen receptor signaling seems important for leukemia B-cell ontogeny, whereas the microenvironment influences B-cell activation, tumor cell lodging, and provision of antigenic stimuli. Using the murine E\u03bc-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells confers proliferative stimuli to leukemia B cells. Intravital imaging revealed a marginal zone B cell\u2013like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin\u2013\u03b2-receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin\/lymphotoxin\u2013\u03b2-receptor signaling or of CXCR5 signaling retards leukemia progression. Thus, CXCR5 activity links tumor cell homing, shaping a survival niche, and access to localized proliferation stimuli.<\/jats:p>\n                  <jats:p>Significance: CLL and other indolent lymphoma are not curable and usually relapse after treatment, a process in which the tumor microenvironment plays a pivotal role. We dissect the consecutive steps of CXCR5-dependent tumor cell lodging and LT\u03b2R-dependent stroma\u2013leukemia cell interaction; moreover, we provide therapeutic solutions to interfere with this reciprocal tumor\u2013stroma cross-talk. Cancer Discov; 4(12); 1448\u201365. \u00a92014 AACR.<\/jats:p>\n                  <jats:p>See related commentary by L\u00f3pez-Guerra et al., p. 1374<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 1355<\/jats:p>","DOI":"10.1158\/2159-8290.cd-14-0096","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T01:40:01Z","timestamp":1411609201000},"page":"1448-1465","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Access to Follicular Dendritic Cells Is a Pivotal Step in Murine Chronic Lymphocytic Leukemia B-cell Activation and Proliferation"],"prefix":"10.1158","volume":"4","author":[{"given":"Kristina","family":"Heinig","sequence":"first","affiliation":[{"name":"1Department of Tumor Genetics and Immunogenetics, Max-Delbr\u00fcck-Center for Molecular Medicine, MDC, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"G\u00e4tjen","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Oncology and Tumorimmunology, Max-Delbr\u00fcck-Center for Molecular Medicine, MDC, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grau","sequence":"additional","affiliation":[{"name":"3Department of Physics, Philipps-University Marburg, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Stache","sequence":"additional","affiliation":[{"name":"1Department of Tumor Genetics and Immunogenetics, Max-Delbr\u00fcck-Center for Molecular Medicine, MDC, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Anagnostopoulos","sequence":"additional","affiliation":[{"name":"4Department of Pathology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Campus Mitte, Berlin, 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