title: Expression pattern of T-cell-associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma.
abstract: Chemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes. (Blood. 2000;96:685-690)
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: O'Hara
authors.forename: M D
authors.initials: MD
authors.lastname: Kraus
authors.forename: A R
authors.initials: AR
authors.lastname: Perez-Atayde
authors.forename: A
authors.initials: A
authors.lastname: Shahsafaei
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: D M
authors.initials: DM
authors.lastname: Dorfman
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000911:Antibodies, Monoclonal; D018925:Chemokines / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000032:analysis; D016399:Lymphoma, T-Cell / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000032:analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; C515355:Ccr4 protein, mouse; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D017730:Ki-1 Antigen; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases