Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+regulatory T cells, evoking antitumor immune responses in humans
Copyright policy )Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+regulatory T cells, evoking antitumor immune responses in humans
SignificanceRegulatory T (Treg) cells expressing the transcription factor FOXP3 play a critical role in suppressing antitumor immune responses. Here we found that, compared with peripheral blood T cells, tumor-infiltrating T cells contained a higher frequency of effector Tregs, which are defined as FOXP3hiand CD45RA−, terminally differentiated, and most suppressive. Effector Treg cells, but not FOXP3loand CD45RA+naïve Treg cells, predominantly expressed C-C chemokine receptor 4 (CCR4) in both cancer tissues and peripheral blood. In vivo or in vitro anti-CCR4 mAb treatment selectively depleted effector Treg cells and efficiently induced tumor-antigen-specific CD4+and CD8+T cells. Thus, cell-depleting anti-CCR4 mAb therapy is instrumental for evoking and enhancing tumor immunity in humans via selectively removing effector-type FOXP3+Treg cells.
- Gulf Coast Regional Blood Center United States
- Osaka University Japan
- Krankenhaus Nordwest Germany
- Tokyo Medical University Japan
Adult, Enzyme-Linked Immunospot Assay, Receptors, CCR4, Antibodies, Monoclonal, Membrane Proteins, Forkhead Transcription Factors, Dendritic Cells, T-Lymphocytes, Regulatory, Statistics, Nonparametric, Gene Expression Regulation, Antigens, Neoplasm, Cell Line, Tumor, Neoplasms, Leukocytes, Mononuclear, Humans, Immunotherapy
Adult, Enzyme-Linked Immunospot Assay, Receptors, CCR4, Antibodies, Monoclonal, Membrane Proteins, Forkhead Transcription Factors, Dendritic Cells, T-Lymphocytes, Regulatory, Statistics, Nonparametric, Gene Expression Regulation, Antigens, Neoplasm, Cell Line, Tumor, Neoplasms, Leukocytes, Mononuclear, Humans, Immunotherapy
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