Increased CCR4 Expression in Cutaneous T Cell Lymphoma

Abstract

Chemokines are critical molecules in leukocyte trafficking, promoting site-specific migration to various tissues. The chemokine receptor CCR4 has recently been associated with skin-homing T cells. In view of the potential importance of CCR4 in skin homing of T cells, we investigated the expression pattern of CCR4 and its ligands TARC/CCL17 and MDC/CCL22 in the peripheral blood and skin of patients with cutaneous T cell lymphoma, a putative malignancy of the skin-homing T cells. In this study we analyzed the pattern of coexpression of the skin-homing molecules cutaneous lymphocyte antigen (CLA) and CCR4 in the blood and skin of patients with cutaneous T cell lymphoma. In the blood of cutaneous T cell lymphoma patients with peripheral blood involvement we found significantly increased percentages of T cells displaying the skin-homing phenotype (CLA+CCR4+) compared with healthy individuals. T cells expressing CLA and CCR4 were also found at high levels in cutaneous T cell lymphoma lesions along with abundant expression of the two CCR4 ligands TARC/CCL17 and MDC/CCL22. These data may explain, in part, why these T cells accumulate in the skin, a diagnostic feature of cutaneous T cell lymphomas.

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

“…Malignant cells in MF express CCR4 and CXCR4. 6,8 In tumor stage MF, CCR4 is down-regulated and expression of CCR7 is induced on CTCL cells. 32 The ligands of CCR7, CCL21, and CCL19 were not up-regulated in MF and therefore cannot hold tumor cells inside the skin.…”

“…Depending on the subtype of CTCL and the stage of the disease, these malignant T cells can express the chemokine receptors CXCR4, CCR4, CCR10, and CCR3. 6,33 The respective ligands CXCL12, 23 CCL17, 7 CCL27, 34 CCL11, 26 and CCL26 27 have been described in CTCL lesional skin and can mediate maintenance of the malignant cells in the skin. Expression of CCL18 by macrophages in PEP, MF patch or plaque stage, and the tumor invasion front of MF lesions might mediate an inhibitory function by abrogating the proliferative effect of other chemokines in CTCL.…”

“…5 CCL17, also known as thymus and activation regulated chemokine, has been described in CTCL skin lesions in association with the infiltration of CCR4 ϩ tumor cells. 6,7 CXCR4, the receptor of CXCL12, is also highly expressed by lesional tumor cells and seems to contribute to the accumulation of tumor cells in the skin. 8 CCL18, previously also designated as DC-derived chemokine 1, pulmonary and activation-regulated chemokine, alternative macrophage activation-associated CC chemokine, or macrophage inflammatory protein 4, is a human chemokine that has no mouse equivalent and the receptor of which is not yet known.…”

Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia

“…CTCLs are not associated with HTLV-1 infection but resemble ATL and frequently express CCR4 (Ferenczi et al, 2002;Kim et al, 2005). Furthermore, CCR4 expression has been shown to be a consistent feature of the large-cell transformation of mycosis fungoides (Jones et al, 2000).…”

CCR10 is expressed in cutaneous T‐cell lymphoma

“…5,6 The importance of chemokines, a group of structurally related small secreted proteins, in the homing of immune cells to sites of inflammation has been well established. 7 Chemokines and their receptors have been associated with tumor metastasis, 8 invasion of lymphatic vessels 9 and possibly trafficking of lymphoma cells.…”