Circulating clonal CLA+ and CD4+ T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7

Sokołowska‐Wojdyło, Małgorzata; Wenzel, Joerg; Gaffal, Evelyn; Lenz, Julia; Speuser, P; Erdmann, Stephan; Abuzahra, Faris; Bowman, Edward P.; Roszkiewicz, Jadwiga; Bieber, Thomas; Tüting, Thomas

doi:10.1111/j.1365-2133.2004.06325.x

Cited by 108 publications

(93 citation statements)

References 25 publications

(50 reference statements)

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“…This immunophenotype resembles that observed for central memory T (T CM ) lymphocytes (8), and thus, as already proposed (6,9), SS cells might represent a neoplastic expansion of this T lymphocytes subset. The mechanisms responsible for skin localization of these neoplastic cells are only partially disclosed: they express adhesion molecules such as cutaneous lymphocyte antigen that initiates skin homing by mediating E-selectin-dependent tethering, rolling, and transmigration within cutaneous venules (10).…”

Section: Introductionmentioning

confidence: 81%

“…In these last years, a number of studies have characterized the circulating neoplastic T lymphocytes of SS as CD45RO+, CCR4+CD26-CD27+CCR7+ cells (3)(4)(5)(6)(7). This immunophenotype resembles that observed for central memory T (T CM ) lymphocytes (8), and thus, as already proposed (6,9), SS cells might represent a neoplastic expansion of this T lymphocytes subset.…”

Section: Introductionmentioning

confidence: 99%

“…An important control mechanism of this complex system is represented by posttranslational regulation involving the storage, release, and presentation of chemokines (13), their structure modification by proteases (14,15) or by homodimeric (16) and heterodimeric complex formation (17,18). Recent studies have already showed that chemokines are strongly involved in MF and SS pathogenesis and neoplastic cell homing to the skin (4)(5)(6)(7)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

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CXCL13 Is Highly Produced by Sézary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines

et al. 2008

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Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression. Furthermore, we show that the addition of CXCL13 to CCL19 or to CCL21, the selective CCR7 agonists responsible for lymph node homing, strongly enhances the migration of CCR7+ SS cells. We also show that neutralization of the CCR7 receptor strongly impairs CCL19/21-induced chemotaxis of SS cells both in the absence or presence of CXCL13. Additional experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of SS cells. Our findings suggest that this newly described CXCL13 expression in SS represents a new pathogenetic mechanism of diagnostic significance. [Cancer Res 2008;68(17):7137-46]

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CXCL13 Is Highly Produced by Sézary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines

et al. 2008

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“…Accordingly, the tumor cells in this disease coexpress the "cutaneous-" and "PLN-"homing signatures, that is, they express L-selectin and CCR7 as well as CLA and CCR4. 59 In line with the strict physiological dichotomy between the skin-and gut-homing memory T-cell populations, neither CTCL expresses the guthoming receptor ␣4␤7. Notably, in adult T-cell leukemia/ lymphoma (ATLL), a systemic lymphoma, CCR4 expression was reported to be linked to skin dissemination.…”

Section: The Dissemination Of T-cell Lymphomasmentioning

confidence: 99%

“…CTCLs usually express the cutaneous lymphocyte-homing receptor CLA 53,54 as well as the chemokine receptor CCR4, often in combination with CCR10 and/or CXCR3. [55][56][57][58][59] The expression of these receptors, not only on tumor cells residing in the skin but also on circulating cells, permits these cells to home effectively to the skin. Interestingly, the tumor cells of mycosis fungoides (MF) and Sézary syndrome, 2 closely related CTCL subtypes, show markedly different homing signatures, which correspond to the distinctive dissemination patterns encountered in these diseases.…”

Section: The Dissemination Of T-cell Lymphomasmentioning

confidence: 99%

Lymphoma dissemination: the other face of lymphocyte homing

Pals

Gorter

Spaargaren

2007

Blood

154

161

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The orchestration of systemic immune responses is critically dependent on coordinated lymphocyte migration and recirculation. This "homing" guides lymphocytes to the microenvironments that control their differentiation and survival, disperses the immunologic repertoire, and targets effector lymphocytes to sites of antigenic insult. Lymphocyte homing is a multistep process that requires chemotaxis and cell adhesion coupled with strategies to overcome physical barriers. At the molecular level, it is regulated by adhesion molecules and chemokines, and facilitated by intrinsic molecular programs that allow "ameboid" shape change, allowing highly effective lymphocyte traffic between different tissue compartments. In case of malignant transformation, however, the fact that lymphocytes are "licensed to move" forms a serious threat to the organism, because it permits rapid tumor dissemination irrespective of the conventional anatomic boundaries limiting early spread in most types of cancer. Thus, unlike the metastatic spread of other cancers, lymphoma dissemination generally is not a reflection of tumor progression but of conserved physiological behavior. The dissemination patterns often reflect basic rules of lymphocyte homing, explaining the strikingly tissue-specific dissemination of, for example, mucosal lymphomas, cutaneous lymphomas, and multiple myeloma. Understanding the molecular mechanisms underlying this behavior may provide novel targets for treatment of lymphoma patients. (Blood.

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Differential Expression of Programmed Death-1 (PD-1) in Sézary Syndrome and Mycosis Fungoides

Çetinözman¹,

Jansen²,

Vermeer³

et al. 2012

Arch Dermatol

116

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Circulating clonal CLA+ and CD4+ T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7

Abstract: Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous 'central' memory T cells in the peripheral blood of these patients.

Cited by 108 publications

References 25 publications

CXCL13 Is Highly Produced by Sézary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines

CXCL13 Is Highly Produced by Sézary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines

Lymphoma dissemination: the other face of lymphocyte homing

Differential Expression of Programmed Death-1 (PD-1) in Sézary Syndrome and Mycosis Fungoides

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