Expression of CCR3 and CCR4 Suggests a Poor Prognosis in Mycosis Fungoides and Sézary Syndrome

Shono, Yuki; Suga, Hiraku; Kamijo, Hiroaki; Fujii, Hikari; Oka, Tomonori; Miyagaki, Tomomitsu; Takahashi‐Shishido, Naomi; Sugaya, Makoto; Sato, Shinichi

doi:10.2340/00015555-3207

Cited by 11 publications

(15 citation statements)

References 15 publications

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“…Since CTCL is a rare disease, and since established criteria for staging and response evaluation for CTCL are limited, few prospective clinical trials for advanced CTCL have been reported, and guidelines for the treatment of CTCL have yet to be established (2, 3). Instead, several preclinical studies have been used to determine the optimal therapy for CTCL (4–6). Among them, Shono et al reported that mycosis fungoides (MF), the most common subtype of CTCL, shows high expression of CCR4 on the cell surface, correlating with poor prognosis of MF (4).…”

Section: Introductionmentioning

confidence: 99%

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Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma

et al. 2019

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Bexarotene is a third-generation retinoid X receptor-selective retinoid that has been approved for use in the treatment of both early and advanced cutaneous T-cell lymphoma (CTCL). Although bexarotene has been used for decades in the treatment of CTCL, little is known about the mechanisms underlying its anti-tumor effects in CTCL patients. This study therefore focused on the immunomodulatory effects of bexarotene in vivo using an EL4 mouse T-cell lymphoma model, followed by investigation in CTCL patients treated with bexarotene. Intraperitoneal injection of bexarotene significantly decreased expressions of CCL22, CXCL5, CXCL10, and p19 in the tumor microenvironment. Based on those results, we then evaluated serum levels of CCL22, CXCL5, and CXCL10 in 25 patients with CTCL, revealing that CCL22 was significantly increased in advanced CTCL compared with early CTCL. Next, we evaluated serum levels of CCL22, CXCL5, and CXCL10 in CTCL patients treated with bexarotene. Serum levels of CCL22 were significantly decreased in 80% of CTCL patients who responded to bexarotene therapy. In addition, immunofluorescence staining revealed CD163+ M2 macrophages as the main source of CCL22. Moreover, bexarotene decreased the production of CCL22 by M2 macrophages generated from monocytes in vitro. Our findings suggest that the clinical benefits of bexarotene are partially attributable to suppressive effects on the production of CCL22 by M2-polarized tumor-associated macrophages.

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Section: Introductionmentioning

confidence: 99%

“…Instead, several preclinical studies have been used to determine the optimal therapy for CTCL (4–6). Among them, Shono et al reported that mycosis fungoides (MF), the most common subtype of CTCL, shows high expression of CCR4 on the cell surface, correlating with poor prognosis of MF (4).…”

Section: Introductionmentioning

confidence: 99%

Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma

et al. 2019

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“…In addition to CCR4 ligands, in this study, we investigated CCL19, CXCL10, and CXCL13, which are described as ligands for CCR7, C‐X‐C Motif Chemokine Receptor (CXCR) CXCR3, and CXCR5, respectively. Notably, these chemokine receptors are also expressed in CTCL cells 13‐15 . No differences were identified in the serum levels of CCL19, CXCL10, or CXCL13 among responders and non‐responders to mogamulizumab therapy, suggesting that CTCL cells in MF might not affect the production of these chemokines.…”

Section: Discussionmentioning

confidence: 95%

“…Notably, these chemokine receptors are also expressed in CTCL cells. [13][14][15] No differences were identified in the serum levels of CCL19, CXCL10, or CXCL13 among responders and non-responders to mogamulizumab therapy, suggesting that CTCL cells in MF might not affect the production of these chemokines.…”

Section: Discussionmentioning

confidence: 96%

Serum CCL22 levels decreased in parallel with disease activity in CCR4 ‐positive mycosis fungoides treated with mogamulizumab

Ohuchi

Fujimura

Lyu

et al. 2020

Dermatologic Therapy

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Mogamulizumab is a humanized anti-CC chemokine receptor type (CCR)4 antibody that shows cytotoxicity against CCR4+ lymphoma cells via antibody-dependent cellmediated cytotoxicity in advanced cutaneous T cell lymphoma (CTCL) patients. The production levels of ligands for CCR4, that is, Chemokine (C-C motif) ligand (CCL)17 and CCL22, are important for the assessment of the disease activity in CTCL patients. We evaluated the serum levels of CCL17, CCL19, CCL22, C-X-C motif chemokine ligand (CXCL)10, and CXCL13, which are ligands for CCR4, CCR7, CCR4, C-X-C

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“…T cell lymphoma In MF and SS, CCR4 + cell numbers increase in parallel with disease progression [128], and higher expression of CCR3 and CCR4 by lymphomatous cells in skin samples is associated with poor survival [141]. In MF, sTARC/ CCL17 were significantly higher in tumor stage than in patch or plaque stage [127].…”

Section: Discussionmentioning

confidence: 99%

What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?

Catherine,

Roufosse

2021

Semin Immunopathol

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Eosinophilic disorders encompass a large spectrum of heterogeneous diseases sharing the presence of elevated numbers of eosinophils in blood and/or tissues. Among these disorders, the role of eosinophils can vary widely, ranging from a modest participation in the disease process to the predominant perpetrator of tissue damage. In many cases, eosinophilic expansion is polyclonal, driven by enhanced production of interleukin-5, mainly by type 2 helper cells (Th2 cells) with a possible contribution of type 2 innate lymphoid cells (ILC2s). Among the key steps implicated in the establishment of type 2 immune responses, leukocyte recruitment toward inflamed tissues is particularly relevant. Herein, the contribution of the chemo-attractant molecule thymus and activation-regulated chemokine (TARC/CCL17) to type 2 immunity will be reviewed. The clinical relevance of this chemokine and its target, C-C chemokine receptor 4 (CCR4), will be illustrated in the setting of various eosinophilic disorders. Special emphasis will be put on the potential diagnostic, prognostic, and therapeutic implications related to activation of the TARC/CCL17-CCR4 axis. Keywords Thymus and activation-regulated chemokine (TARC) . CCL17 . C-C chemokine receptor 4 (CCR4) . Eosinophils . Eosinophilic disorders . Hypereosinophilic syndromes Abbreviations AA Allergic asthma ABPA Allergic bronchopulmonary aspergillosis ADCC Antibody-dependent cell cytotoxicity AEC Absolute eosinophil count AEP Acute eosinophilic pneumonia AITL Angioimmunoblastic T cell lymphoma ALI Acute lung injury ANCA Anti-neutrophil cytoplasmic antibody ARDS Acute respiratory distress syndrome ATLL Adult T cell leukemia/lymphoma AUC Area under the curve BALF Bronchoalveolar lavage fluid This article is a contribution to the Special issue on: Eosinophils -Guest

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Expression of CCR3 and CCR4 Suggests a Poor Prognosis in Mycosis Fungoides and Sézary Syndrome

Cited by 11 publications

References 15 publications

Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma

Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma

Serum CCL22 levels decreased in parallel with disease activity in CCR4 ‐positive mycosis fungoides treated with mogamulizumab

What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?

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