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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 685-690
Expression pattern of T-cell-associated chemokine receptors and
their chemokines correlates with specific subtypes of T-cell
non-Hodgkin lymphoma
Dan Jones,
Carl O'Hara,
Madeleine D. Kraus,
Antonio R. Perez-Atayde,
Aliakbar Shahsafaei,
Lijun Wu, and
David M. Dorfman
From the Department of Pathology, Brigham and Women's Hospital and
Harvard Medical School; the Department of Pathology, Boston Medical
Center; the Department of Pathology, Children's Hospital, Boston; the
Department of Pathology, LeukoSite, Inc, Cambridge, MA; and the
Department of Pathology, Washington University School of Medicine, St
Louis, MO.
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.
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