PMID- 27177223
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20190221
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 25
DP  - 2016 Jun 21
TI  - Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory 
      cells evokes an antitumor immune response in head and neck squamous cell 
      carcinoma.
PG  - 37714-37727
LID - 10.18632/oncotarget.9265 [doi]
AB  - FoxP3+ regulatory T (Treg) cells have diverse functions in the suppression of 
      antitumor immunity. We show that FoxP3hiCD45RA-CD4+ Treg cells [activated Treg 
      (aTreg) cells] are the predominant cell population among tumor-infiltrating 
      FoxP3+ T cells, and that high aTreg cell-infiltrating content is associated with 
      reduced survival in patients with head and neck squamous cell carcinoma (HNSCC). 
      In vitro studies have demonstrated that aTreg cells can suppress tumor-associated 
      antigen (TAA) effector T cell immune responses in HNSCC. Moreover, C-C chemokine 
      receptor 4 (CCR4) was specifically expressed by aTreg cells in the peripheral 
      blood of HNSCC patients. Using a RayBiotech human chemokine antibody array, we 
      showed that monocyte chemoattractant protein-1 (MCP-1), an endogenous 
      CCR4-binding ligand, was specifically upregulated in the HNSCC microenvironment 
      compared to the other four CCR4-binding ligands. Blocking MCP-1/CCR4 
      signaling-induced aTreg cell recruitment using a CCR4 antagonist evoked antitumor 
      immunity in mice, and lead to inhibition of tumor growth and prolonged survival. 
      Therefore, blocking aTreg cell trafficking in tumors using CCR4-binding agents 
      may be an effective immunotherapy for HNSCC.
FAU - Sun, Wei
AU  - Sun W
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Li, Wei-Jin
AU  - Li WJ
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Wei, Fan-Qin
AU  - Wei FQ
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The Sixth Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
FAU - Wong, Thian-Sze
AU  - Wong TS
AD  - Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
FAU - Lei, Wen-Bin
AU  - Lei WB
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Zhu, Xiao-Lin
AU  - Zhu XL
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Li, Jian
AU  - Li J
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Wen, Wei-Ping
AU  - Wen WP
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital, Sun Yat-sen University, Guangzhou, China.
AD  - Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, 
      Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR4 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Receptors, CCR4)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Antigens, Neoplasm/metabolism
MH  - Antineoplastic Agents/*pharmacology
MH  - CD4-Positive T-Lymphocytes/cytology
MH  - Carcinoma, Squamous Cell/*drug therapy/*immunology/therapy
MH  - Chemokine CCL2/*antagonists & inhibitors
MH  - Female
MH  - Forkhead Transcription Factors/metabolism
MH  - Head and Neck Neoplasms/*drug therapy/*immunology/therapy
MH  - Humans
MH  - Immune System
MH  - Leukocyte Common Antigens/metabolism
MH  - Leukocytes, Mononuclear/cytology
MH  - Lymphocytes, Tumor-Infiltrating/cytology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Middle Aged
MH  - Neoplasm Transplantation
MH  - Prognosis
MH  - Receptors, CCR4/*antagonists & inhibitors
MH  - Signal Transduction
MH  - Squamous Cell Carcinoma of Head and Neck
PMC - PMC5122343
OTO - NOTNLM
OT  - CCR4
OT  - Treg
OT  - antitumor immunity
OT  - head and neck squamous cell carcinoma
OT  - prognosis
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2016/10/23 06:00
MHDA- 2018/01/18 06:00
PMCR- 2016/06/21
CRDT- 2016/05/14 06:00
PHST- 2016/01/28 00:00 [received]
PHST- 2016/04/26 00:00 [accepted]
PHST- 2016/10/23 06:00 [pubmed]
PHST- 2018/01/18 06:00 [medline]
PHST- 2016/05/14 06:00 [entrez]
PHST- 2016/06/21 00:00 [pmc-release]
AID - 9265 [pii]
AID - 10.18632/oncotarget.9265 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Jun 21;7(25):37714-37727. doi: 10.18632/oncotarget.9265.