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PLoS One. 2013 Sep 2;8(9):e73952. doi: 10.1371/journal.pone.0073952. eCollection 2013.

Depletion of CD4+ CD25+ regulatory T cells promotes CCL21-mediated antitumor immunity.

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Department of Histology and Embryology, Tongji University School of Medicine, Shanghai, China.

Erratum in

  • PLoS One. 2014;9(3):e93126. Chen, Long [added]; Qin, Jie [added]; Li, Rilun [added]; Liu, Binbin [added]; She, Zhenjue [added]; Zhong, Cuiping [added]; Liang, Chunmin [added].


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.

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