Interleukin-7 is a growth factor for Sézary lymphoma cells.

Dalloul, Ali; Laroche, Liliane; Bagot, Martine; Mossalayi, M. Djavad; Fourcade, C.; Thacker, D J; Hogge, Donna E.; Merle-Béral, Hélène; Debré, Patrice; Schmitt, C.

doi:10.1172/jci115920

Cited by 148 publications

(72 citation statements)

References 36 publications

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“…12,24,32 IL-17 therefore does not behave like other cytokines such as IL-2, IL-7 and IL-15, whose receptors share the same ␥ chain and are considered to be growth factors for normal T cells and Sezary cells. [33][34][35] This difference may be explained by the fact that the IL-17 receptor does not belong to the cytokine receptor family associated with the ␥ chain.…”

Section: Discussionmentioning

confidence: 99%

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4 ؉ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3 ؉ CD4 ؉ CD45RO ؉ , a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.

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Section: Discussionmentioning

confidence: 99%

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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“…The establishment of long-term CTCL cell lines is challenging, as these cell frequently undergo spontaneous cell death during in vitro culture [37,38] (and personal observation). Therefore, the resistance to apoptosis observed in vivo is unlikely due to an intrinsic resistance to apoptosis alone.…”

Section: Immunopathogenesismentioning

confidence: 99%

“…Therefore, the resistance to apoptosis observed in vivo is unlikely due to an intrinsic resistance to apoptosis alone. Rather, extrinsic factors present within the tumor microenvironment likely contribute to the growth and survival of malignant T cells, a contention supported by the observation that cytokine supplementation or the provision of T-cell costimulatory signals supports the growth of malignant T cells in vitro [37,39,40]. Both gene-expression profiling and immunohistochemistry-based studies have recently highlighted the important contribution of nonmalignant cells, including monocyte-derived lymphoma-associated macrophages, in the pathogenesis of both Hodgkin and non-Hodgkin lymphomas [41][42][43].…”

Section: Immunopathogenesismentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

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“…24,25 IL-7 is also involved in the growth and survival of Sézary cells. 27,28 Because CTCL cells may remain restricted to the skin during the course of the disease, locally produced IL-7 may be important for the survival of T cells.In this study, we investigated plasma IL-7 levels in 93 CTCL patients and further measured lesional IL-7 mRNA expression levels in skin lesions from 10 CTCL patients; both were compared with normal plasma and skin, respectively. In addition, we cultured For personal use only.…”

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confidence: 99%

Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma

Yamanaka

Clark

Rich

et al. 2006

Blood

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Cutaneous T-cell lymphomas (CTCLs) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skinhoming T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL. IntroductionCutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoproliferative disorders of the skin 1 and are regarded as a subset of extranodal non-Hodgkin T-cell lymphomas of skinhoming memory T cells. 2 Among CTCL patients with peripheral blood involvement, there are greater numbers of T cells expressing the skin-homing cutaneous lymphocyte antigen (CLA) and the chemokine receptor CCR4 than are present in healthy donors. 3 Furthermore, the CCR4 ligand CCL17 is highly expressed on the endothelial cells in CTCL skin lesions. 3 These findings, together with the increased expression of E selectin and ICAM-1 in CTCL lesions, 4,5 suggest that the appropriate microenvironment exists for the entry of skin-homing T cells into CTCL lesions. 3 These malignant T cells may be found singly or collectively within the epidermis and admixed with an infiltrate of mononuclear cells within the papillary dermis underlying the involved epidermis.We recently reported that in all cases of advanced CTCL, and many cases of early disease, there is a significant disruption of the diversity of the T-cell repertoire in peripheral blood. 6 T-cell receptor beta-variable (BV) spectratyping revealed diminished complexity in many BV families, 6 and this correlated with diminished T-cell receptor excision circle (TREC) levels. 7 Both observations are consistent with the idea that some normal T cells are being removed from circulation and other T cells are proliferating to fill the space that this removal creates in the T-cell compartment. The idea that there may be a proliferative stimulus in the peripheral blood of CTCL patients led us to examine peripheral blood plasma for the presence of T-cell trophic cytokines Patients and healthy controls were studied, and plasma levels of interleukin-2 (IL-2), IL-4, IL-7, IL-12, IL-13, ...

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Interleukin-7 is a growth factor for Sézary lymphoma cells.

Cited by 148 publications

References 36 publications

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma

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