Expression pattern of T-cell-associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma

Chemokine receptors mediate the migration of lymphocytes through the bindin g of soluble ligands, and their expression is differentially regulated in l ymphocyte subsets. The pattern of chemokine receptor expression in T-cell n on-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of th e Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymph oma, and we studied the receptors CCR4 and CCR5 and some of their ligands i n a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric ly mphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and uns pecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only I of 15 patients with anaplastic lymphoma kinase (ALK)-positive anapl astic large-cell lymphoma. In contrast, all ALK-positive tumors showed diff use 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 ligan d), and MCP-P (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 nor mal T-cell subsets, we demonstrated that there is frequent differential exp ression of chemokine receptors in T-cell tumors, which may explain, in part , the distinctive patterns of spread in different tumor subtypes. (C) 2000 by The American Society of Hematology.