Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma
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...
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doaj-ccdc7ff2acfd4e738cd501f1761544592020-11-25T01:54:30ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-09-01910.3389/fonc.2019.00907468903Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell LymphomaKayo Tanita0Taku Fujimura1Yota Sato2Chunbing Lyu3Yumi Kambayashi4Dai Ogata5Satoshi Fukushima6Azusa Miyashita7Hideki Nakajima8Motoki Nakamura9Akimichi Morita10Setsuya Aiba11Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Dermatology, Saitama Medical University, Saitama, JapanDepartment of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanDepartment of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanDepartment of Dermatology, Kochi Medical School, Kochi University, Kochi, JapanDepartment of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanBexarotene 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.https://www.frontiersin.org/article/10.3389/fonc.2019.00907/fulladvanced CTCLbexarotenetumor-associated macrophagesCCL22immunomodulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kayo Tanita Taku Fujimura Yota Sato Chunbing Lyu Yumi Kambayashi Dai Ogata Satoshi Fukushima Azusa Miyashita Hideki Nakajima Motoki Nakamura Akimichi Morita Setsuya Aiba |
spellingShingle |
Kayo Tanita Taku Fujimura Yota Sato Chunbing Lyu Yumi Kambayashi Dai Ogata Satoshi Fukushima Azusa Miyashita Hideki Nakajima Motoki Nakamura Akimichi Morita Setsuya Aiba Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma Frontiers in Oncology advanced CTCL bexarotene tumor-associated macrophages CCL22 immunomodulation |
author_facet |
Kayo Tanita Taku Fujimura Yota Sato Chunbing Lyu Yumi Kambayashi Dai Ogata Satoshi Fukushima Azusa Miyashita Hideki Nakajima Motoki Nakamura Akimichi Morita Setsuya Aiba |
author_sort |
Kayo Tanita |
title |
Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma |
title_short |
Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma |
title_full |
Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma |
title_fullStr |
Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma |
title_full_unstemmed |
Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma |
title_sort |
bexarotene reduces production of ccl22 from tumor-associated macrophages in cutaneous t-cell lymphoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2019-09-01 |
description |
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. |
topic |
advanced CTCL bexarotene tumor-associated macrophages CCL22 immunomodulation |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.00907/full |
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