CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer/T-cell lymphoma.
CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer/T-cell lymphoma.
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DOI：
10.1007/s00262-015-1675-7
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Harabuchi Y
中科院分区：
文献类型：
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作者：
Kumai T;Nagato T;Kobayashi H;Komabayashi Y;Ueda S;Kishibe K;Ohkuri T;Takahara M;Celis E;Harabuchi Y
鼻自然杀伤/ t细胞淋巴瘤（NNKTL）与eb病毒相关，由于局部侵袭和/或多发传播，预后较差。多种趋化因子在肿瘤增殖和侵袭中发挥作用，包括C-C趋化因子受体4 （CCR4）在内的趋化因子受体被认为是治疗血液系统恶性肿瘤的潜在靶点。本研究的目的是确定NNKTL是否产生特定的趋化因子。采用趋化因子蛋白阵列法和ELISA法比较了NNKTL细胞培养上清液中趋化因子与其他淋巴瘤或白血病细胞的表达规律。趋化因子（C-C基序）配体（CCL） 17和CCL22在NNKTL细胞系中的产生量高于其他细胞系。此外，CCL17和CCL22在NNKTL患者血清中也很容易观察到。患者体内这些趋化因子的水平明显高于健康对照组。此外，我们检测了CCR4 （CCL17和CCL22的受体）在NNKTL细胞株表面和NNKTL患者组织中的表达。抗ccr4单克隆抗体（mAb）有效诱导自然杀伤细胞介导的NNKTL细胞株抗体依赖细胞毒性。我们的研究结果表明，CCL17和CCL22可能是NNKTL发展的重要因素，并为使用抗ccr4单抗免疫治疗这种淋巴瘤开辟了可能性。
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.