Antagonization of CCR4 leads to failure of activated regulatory T-cell migration in a mice model of head and neck squamous cell carcinoma

被引：0
作者：
Li, Wei-Jin [1 ,2 ]
Sun, Wei [1 ]
We, Fan-Qin [1 ,3 ]
Wen, Wei-Ping [1 ]
机构：
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Otorhinolaryngol Head & Neck Surg, 58 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Otorhinolaryngol Head & Neck Surg, Guangzhou, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Otorhinolaryngol Head & Neck Surg, Guangzhou, Guangdong, Peoples R China
来源：
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2018年 / 11卷 / 09期
基金：
中国国家自然科学基金;
关键词：
CCR4; tumor microenvironment; activated Treg; mouse; head and neck squamous cell carcinoma; antagonist; DENILEUKIN DIFTITOX; ANTITUMOR IMMUNITY; ANTI-CCR4; ANTIBODY; CANCER-PATIENTS; TUMOR-IMMUNITY; PROGRESSION; RECRUITMENT; DEPLETION; SUBSETS; TREG;
D O I：
暂无
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
By mediating immune tolerance in head and neck squamous cell carcinomas (HNSCC), regulatory T-cells (Tregs) are not functionally heterogeneous. Animal models of HNSCC regarding CD4(+)CD45RA(-)CD25(+++) Treg cells [activated Treg (aTreg) cells] have not been reported, making it difficult to target tumor-infiltrating aTregs. This present study confirmed that mice aTreg cells, with suppressive capacity, were dramatically increased in the tumor microenvironment. Moreover, C-C chemokine receptor 4 (CCR4) was specifically expressed by aTreg cells while MCP-1 (CCL2), CCL17 (TARC), CCL22 (MDC), and endogenous CCR4 binding ligands were upregulated in the tumor microenvironment. An in vitro study showed that aTreg migration was successfully blocked after use of a CCR4 antagonist. Therefore, blocking the recruitment of aTreg cells induced by CCR4 is a promising method for future studies on immunotherapy for HNSCC.
引用
收藏
页码：9333 / 9342
页数：10
相关论文
共 26 条
[1]   Regulatory T cells: What role do they play in antitumor immunity in patients with head and neck cancer? [J].
Alhamarneh, Osama ;
Amarnath, Shoba M. P. ;
Stafford, Nicholas D. ;
Greenman, John .
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2008, 30 (02) :251-261
[2]   Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma [J].
Attia, P ;
Maker, AV ;
Haworth, LR ;
Rogers-Freezer, L ;
Rosenberg, SA .
JOURNAL OF IMMUNOTHERAPY, 2005, 28 (06) :582-592
[3]  
Baecher-Allan CM, 2005, CLIN IMMUNOL, V117, P192, DOI 10.1016/j.clim.2005.08.008
[4]   FOXP3 gene polymorphism is associated with hepatitis B-related hepatocellular carcinoma in China [J].
Chen, YanHui ;
Zhang, HengHui ;
Liao, WeiJia ;
Zhou, JinXue ;
He, GaiXia ;
Xie, XingWang ;
Fei, Ran ;
Qin, LiLing ;
Wei, Lai ;
Chen, HongSong .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2013, 32
[5]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[6]   Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells [J].
Dannull, J ;
Su, Z ;
Rizzieri, D ;
Yang, BK ;
Coleman, D ;
Yancey, D ;
Zhang, AJ ;
Dahm, P ;
Chao, N ;
Gilboa, E ;
Vieweg, J .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (12) :3623-3633
[7]   Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma [J].
Duvic, Madeleine ;
Pinter-Brown, Lauren C. ;
Foss, Francine M. ;
Sokol, Lubomir ;
Jorgensen, Jeffrey L. ;
Challagundla, Pramoda ;
Dwyer, Karen M. ;
Zhang, Xiaoping ;
Kurman, Michael R. ;
Ballerini, Rocco ;
Liu, Li ;
Kim, Youn H. .
BLOOD, 2015, 125 (12) :1883-1889
[8]   Medical progress - Head and neck cancer [J].
Forastiere, A ;
Koch, W ;
Trotti, A ;
Sidransky, D .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (26) :1890-1900
[9]   Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4+CD25+ regulatory T cells [J].
Iellem, A ;
Mariani, M ;
Lang, R ;
Recalde, H ;
Panina-Bordignon, P ;
Simigaglia, F ;
D'Ambrosio, D .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (06) :847-853
[10]   The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and cancer [J].
Khazaie, K ;
von Boehmer, H .
SEMINARS IN CANCER BIOLOGY, 2006, 16 (02) :124-136
123