Data from Access to Follicular Dendritic Cells Is a Pivotal Step in Murine Chronic Lymphocytic Leukemia B-cell Activation and Proliferation Article Swipe
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· 2023
· Open Access
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· DOI: https://doi.org/10.1158/2159-8290.c.6546089.v1
· OA: W4392702701
<div>Abstract<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 <i>Eμ-Tcl1</i> 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–like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin–β-receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin/lymphotoxin–β-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.</p><p><b>Significance:</b> 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 LTβR-dependent stroma–leukemia cell interaction; moreover, we provide therapeutic solutions to interfere with this reciprocal tumor–stroma cross-talk. <i>Cancer Discov; 4(12); 1448–65. ©2014 AACR</i>.</p><p>See related commentary by López-Guerra et al., p. 1374</p><p>This article is highlighted in the In This Issue feature, p. 1355</p></div>
