Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+regulatory T cells, evoking antitumor immune responses in humans

Significance Regulatory 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 FOXP3 hi and CD45RA − , terminally differentiated, and most suppressive. Effector Treg cells, but not FOXP3 lo and 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.