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Jun 21, 2016;7 (25): 37714-37727.

Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma.

Wei Sun, Wei-Jin Li, Fan-Qin Wei, Thian-Sze Wong, Wen-Bin Lei, Xiao-Lin Zhu, Jian Li, Wei-Ping Wen
Author Information
  1. Wei Sun: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  2. Wei-Jin Li: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  3. Fan-Qin Wei: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  4. Thian-Sze Wong: Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
  5. Wen-Bin Lei: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  6. Xiao-Lin Zhu: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  7. Jian Li: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  8. Wei-Ping Wen: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
PMID: 27177223 DOI: 10.18632/oncotarget.9265

Abstract

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.

Keywords

CCR4 Treg antitumor immunity head and neck squamous cell carcinoma prognosis

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MeSH Term

Aged
Animals
Antigens, Neoplasm
Antineoplastic Agents
CD4-Positive T-Lymphocytes
Carcinoma, Squamous Cell
Chemokine CCL2
Female
Forkhead Transcription Factors
Head and Neck Neoplasms
Humans
Immune System
Leukocyte Common Antigens
Leukocytes, Mononuclear
Lymphocytes, Tumor-Infiltrating
Male
Mice
Mice, Inbred C3H
Middle Aged
Neoplasm Transplantation
Prognosis
Receptors, CCR4
Signal Transduction
Squamous Cell Carcinoma of Head and Neck

Chemicals

Antigens, Neoplasm
Antineoplastic Agents
CCL2 protein, human
CCR4 protein, human
Chemokine CCL2
FOXP3 protein, human
Forkhead Transcription Factors
Receptors, CCR4
Leukocyte Common Antigens
Journal Article

Word Cloud

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