Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma
| Autor: | Fanqin Wei, Weiping Wen, Wei-Jin Li, Thian-Sze Wong, Jian Li, Wei Sun, Xiaolin Zhu, Wenbin Lei |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male 0301 basic medicine Chemokine medicine.medical_treatment Mice 0302 clinical medicine Medicine Chemokine CCL2 Mice Inbred C3H education.field_of_study biology FOXP3 Forkhead Transcription Factors Middle Aged Prognosis Treg medicine.anatomical_structure Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis Carcinoma Squamous Cell Female Signal Transduction Research Paper Receptors CCR4 antitumor immunity T cell Population Antineoplastic Agents head and neck squamous cell carcinoma 03 medical and health sciences Lymphocytes Tumor-Infiltrating Immune system Antigen Antigens Neoplasm Animals Humans education Aged Squamous Cell Carcinoma of Head and Neck business.industry Immunotherapy medicine.disease Head and neck squamous-cell carcinoma 030104 developmental biology Immune System Immunology Leukocytes Mononuclear Cancer research biology.protein Leukocyte Common Antigens CCR4 business Neoplasm Transplantation |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Wei Sun 1, 2 , Wei-Jin Li 1, 2 , Fan-Qin Wei 1, 2, 3 , Thian-Sze Wong 4 , Wen-Bin Lei 1, 2 , Xiao-Lin Zhu 1, 2 , Jian Li 1, 2 , Wei-Ping Wen 1, 2 1 Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 2 Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-Sen University, Guangzhou, China 3 Department of Otorhinolaryngology-Head and Neck Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 4 Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China Correspondence to: Wei-Ping Wen, email: wenwp@mail.sysu.edu.cn Wei Sun, email: sunw2@mail2.sysu.edu.cn Keywords: CCR4, Treg, antitumor immunity, prognosis, head and neck squamous cell carcinoma Received: January 28, 2016 Accepted: April 26, 2016 Published: May 10, 2016 ABSTRACT FoxP3 + regulatory T (Treg) cells have diverse functions in the suppression of antitumor immunity. We show that FoxP3 hi CD45RA − 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. |
| Databáze: | OpenAIRE |
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