title: Depletion of CD4+ CD25+ regulatory T cells promotes CCL21-mediated antitumor immunity.
abstract: CCL21 is known to attract dendritic cells (DCs) and T cells that may reverse tumor-mediated immune suppression. The massive infiltration of tumors by regulatory T cells (Tregs) prevents the development of a successful helper immune response. In this study, we investigated whether elimination of CD4(+) CD25(+) Tregs in the tumor microenvironment using anti-CD25 monoclonal antibodies (mAbs) was capable of enhancing CCL21-mediated antitumor immunity in a mouse hepatocellular carcinoma (HCC) model. We found that CCL21 in combination with anti-CD25 mAbs (PC61) resulted in improved antitumor efficacy and prolonged survival, not only inhibited tumor angiogenesis and cell proliferation, but also led to significant increases in the frequency of CD4(+), CD8(+) T cells and CD11c(+) DCs within the tumor, coincident with marked induction of tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) at the local tumor site. The intratumoral immune responses were accompanied by the enhanced elaboration of IL-12 and IFN-γ, but reduced release of the immunosuppressive mediators IL-10 and TGF-β1. The results indicated that depletion of Tregs in the tumor microenvironment could enhance CCL21-mediated antitumor immunity, and CCL21 combined with anti-CD25 mAbs may be a more effective immunotherapy to promote tumor rejection.
authors.affiliation: Department of Histology and Embryology, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhou
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.forename: Rilun
authors.initials: R
authors.lastname: Li
authors.forename: Huihong
authors.initials: H
authors.lastname: Tao
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhen
authors.forename: Haixia
authors.initials: H
authors.lastname: Chen
authors.forename: Guolin
authors.initials: G
authors.lastname: Chen
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Yang
authors.forename: Binbin
authors.initials: B
authors.lastname: Liu
authors.forename: Zhenjue
authors.initials: Z
authors.lastname: She
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhong
authors.forename: Chunmin
authors.initials: C
authors.lastname: Liang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D039521:CD11c Antigen / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054421:Chemokine CCL21 / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D039521:CD11c Antigen; D054421:Chemokine CCL21; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D018664:Interleukin-12; D007371:Interferon-gamma
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