Abstract
According to the classical paradigm, CCR7 is a homing chemokine receptor that grants normal lymphocytes access to secondary lymphoid tissues such as lymph nodes or spleen. As such, in most lymphoproliferative disorders, CCR7 expression correlates with nodal or spleen involvement. Nonetheless, recent evidence suggests that CCR7 is more than a facilitator of lymphatic spread of tumor cells. Here, we review published data to catalogue CCR7 expression across blood cancers and appraise which classical and novel roles are attributed to this receptor in the pathogenesis of specific hematologic neoplasms. We outline why novel therapeutic strategies targeting CCR7 might provide clinical benefits to patients with CCR7-positive hematopoietic tumors.
Highlights
Lymph nodes (LN) function as major immunological hubs, being essential for immune homeostasis and the generation of effective immune responses [1]
chemokine receptor 7 (CCR7) directs central aspects of immune cell migration into the LN: cell trafficking, firm arrest at the endothelium, extravasation, positioning within secondary lymphoid organs (SLO), activation, differentiation, survival, and egress. All these processes mediated by CCR7 take place upon binding to either of its two cognate ligands, the chemokines CCL19 and CCL21, which are constitutively expressed by stroma cells in SLO and which are present on lymphatic vessels, highendothelial venules (HEVs), and fibroblastic reticular cells (FBR) of the T-cell zones [5, 6, 11]
CCR7 gene expression could not be significantly correlated with lymphoid organ involvement or patient survival in Sézary syndrome (SS) [179], it appears plausible that production of CCL19 and CCL21 by stromal and endothelial cells in lymphoid tissues contributes to the lymphotropism of SS cells
Summary
Lymph nodes (LN) function as major immunological hubs, being essential for immune homeostasis and the generation of effective immune responses [1]. LNs are fundamental sites-of-origin in disease development and progression as well as in treatment failure of several hematological malignancies. Growing evidence suggests that cell trafficking orchestrated by the C-C chemokine receptor 7 (CCR7) plays a critical role in the pathophysiology of several leukemias and lymphomas. This receptor assists malignant cells in access to niches that provide proliferating cues and enable escape from therapy-induced death, promoting disease progression and resistance. We further appraise how this chemokine receptor is of great potential for the development of rational and effective therapies in some of these conditions
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