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 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)
Jones
D
D
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
O'Hara
C
C
Kraus
M D
MD
Perez-Atayde
A R
AR
Shahsafaei
A
A
Wu
L
L
Dorfman
D M
DM
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
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