Depletion of Tregs in vivo: a promising approach to enhance antitumor immunity without autoimmunity

Abstract

Evaluation of: Rech AJ, Mick R, Martin S et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patents. Sci. Transl. Med. 4(134), 134ra62 (2012). Tregs are involved in the maintenance of immunological self-tolerance. Recent studies have revealed that Tregs suppress antitumor immunity and that they are major obstacles for cancer immunotherapy. Various approaches have been carried out to cancel immunological suppression by Tregs in clinical settings; however, side effects such as autoimmunity occurred and expected antitumor effects were not achieved. In a recent study, Rech et al. evaluated daclizumab, a US FDA-approved humanized anti-CD25 antibody, for regulation of Treg cells in a peptide vaccination trial of breast cancer patients. Daclizumab caused long-lasting depletion of CD25+ Tregs, reprogramming of CD25+ Tregs, and enhancement of antipeptide immune response. Of note, major autoimmune responses were not observed in daclizumab-treated patients. This study provides a possible safe and promising approach to regulate Tregs in cancer vaccine therapy.