CCR4 is rarely expressed in CCR4-mutated T/NK-cell lymphomas other than adult T-cell leukemia/lymphoma

Sakamoto, Yuma; Fujii, Keiichiro; Murase, Shunji; Nakano, Satsuki; Awata, Masaki; Murase, Takayuki; Kusumoto, Shigeru; Iida, Shinsuke; Utsunomiya, Atae; Ueda, Ryuzo; Ishida, Takashi; Inagaki, Hiroshi

doi:10.1007/s12185-019-02728-5

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…One reason for low response to Mogamulizumab is obviously the low or negative surface expression of CCR4 on malignant T cells. In one study, it was reported that CCR4 was positive in 48/52 (92%) of ATL cases [ 243 ]. The fact that the C-terminal truncation of CCR4, which leads to the high constitutive surface expression of CCR4, correlates with the superior efficacy of Mogamulizumab supports this notion [ 150 , 244 ].…”

Section: Discussionmentioning

confidence: 99%

CCR4 as a Therapeutic Target for Cancer Immunotherapy

Yoshie

2021

Cancers

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CCR4 is a chemokine receptor mainly expressed by T cells. It is the receptor for two CC chemokine ligands, CCL17 and CCL22. Originally, the expression of CCR4 was described as highly selective for helper T type 2 (Th2) cells. Later, its expression was extended to other T cell subsets such as regulatory T (Treg) cells and Th17 cells. CCR4 has long been regarded as a potential therapeutic target for allergic diseases such as atopic dermatitis and bronchial asthma. Furthermore, the findings showing that CCR4 is strongly expressed by T cell malignancies such as adult T cell leukemia/lymphoma (ATLL) and cutaneous T cell lymphomas (CTCLs) have led to the development and clinical application of the fully humanized and glyco-engineered monoclonal anti-CCR4 Mogamulizumab in refractory/relapsed ATLL and CTCLs with remarkable successes. However, Mogamulizumab often induces severe adverse events in the skin possibly because of its efficient depletion of Treg cells. In particular, treatment with Mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo-HSCT), the only curative option of these T cell malignancies, often leads to severe glucocorticoid-refractory graft-versus-host diseases. The efficient depletion of Treg cells by Mogamulizumab has also led to its clinical trials in advanced solid tumors singly or in combination with immune checkpoint inhibitors. The main focus of this review is CCR4; its expression on normal and malignant T cells and its significance as a therapeutic target in cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%