title: CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma.
abstract: CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma.
authors.affiliation: Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Food Science and Nutrition, Kindai University Faculty of Agriculture, Nara, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koyama
authors.affiliation: Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.
authors.forename: Reira
authors.initials: R
authors.lastname: Imamura
authors.affiliation: Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Division of Computational Drug Design and Discovery, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nishiwaki
authors.affiliation: Department of Dermatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oiso
authors.affiliation: Department of Dermatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.affiliation: Department of Microbiology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.affiliation: Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan. Electronic address: nakayama@phar.kindai.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054422:Chemokine CCL22 / Q000378:metabolism; D003606:Dacarbazine / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005838:Genotype; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D054398:Receptors, CCR4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D018906:Antineoplastic Agents, Alkylating; C515483:Ccl22 protein, mouse; C515355:Ccr4 protein, mouse; D054422:Chemokine CCL22; D054398:Receptors, CCR4; D003606:Dacarbazine
keywords: CCR4; Chemokine; Melanoma; Th17; Treg