title: CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer/T-cell lymphoma.
abstract: Nasal natural killer/T-cell lymphoma (NNKTL) is associated with Epstein-Barr virus and has a poor prognosis because of local invasion and/or multiple dissemination. Various chemokines play a role in tumor proliferation and invasion, and chemokine receptors including the C-C chemokine receptor 4 (CCR4) are recognized as potential targets for treating hematologic malignancies. The aim of the present study was to determine whether specific chemokines are produced by NNKTL. We compared chemokine expression patterns in culture supernatants of NNKTL cell lines with those of other lymphoma or leukemia cell lines using chemokine protein array and ELISA. Chemokine (C-C motif) ligand (CCL) 17 and CCL22 were highly produced by NNKTL cell lines as compared to the other cell lines. In addition, CCL17 and CCL22 were readily observed in the sera of NNKTL patients. The levels of these chemokines were significantly higher in patients than in healthy controls. Furthermore, we detected the expression of CCR4 (the receptor for CCL17 and CCL22) on the surface of NNKTL cell lines and in tissues of NNKTL patients. Anti-CCR4 monoclonal antibody (mAb) efficiently induced antibody-dependent cellular cytotoxicity mediated by natural killer cells against NNKTL cell lines. Our results suggest that CCL17 and CCL22 may be important factors in the development of NNKTL and open up the possibility of immunotherapy of this lymphoma using anti-CCR4 mAb.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kumai
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Komabayashi
authors.forename: Seigo
authors.initials: S
authors.lastname: Ueda
authors.forename: Kan
authors.initials: K
authors.lastname: Kishibe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohkuri
authors.forename: Miki
authors.initials: M
authors.lastname: Takahara
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
mesh_terms: D054414:Chemokine CCL17 / Q000276:immunology*; D054422:Chemokine CCL22 / Q000276:immunology*; D018925:Chemokines; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D054391:Lymphoma, Extranodal NK-T-Cell / Q000276:immunology* / Q000628:therapy*; D016399:Lymphoma, T-Cell; D058990:Molecular Targeted Therapy; D054398:Receptors, CCR4 / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018925:Chemokines; D054398:Receptors, CCR4