title: Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma.
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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.|Department of Otorhinolaryngology-Head and Neck Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Fan-Qin
authors.initials: FQ
authors.lastname: Wei
authors.affiliation: Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Thian-Sze
authors.initials: TS
authors.lastname: Wong
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Lei
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wen
mesh_terms: D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology* / Q000628:therapy; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007107:Immune System; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011379:Prognosis; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C111835:CCL2 protein, human; C515354:CCR4 protein, human; D018932:Chemokine CCL2; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054398:Receptors, CCR4; D017493:Leukocyte Common Antigens
keywords: CCR4; Treg; antitumor immunity; head and neck squamous cell carcinoma; prognosis