title: Tumor-associated dendritic cells: molecular mechanisms to suppress antitumor immunity.
abstract: Evaluation of: Watkins SK, Zhu Z, Riboldi E et al. FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer. J. Clin. Invest. 121(4), 1361-1372 (2011). Tumor-associated dendritic cells (TADCs) have been described as immune-suppressive cells in cancers, and part of the molecular mechanisms has emerged. The transcription factor FOXO3--one of the tumor suppressors--is overexpressed in TADCs that have been infiltrated in human prostate cancers and TRAMP mouse model of prostate cancers, and induces the expression of immune-suppressive genes including indoleamine-2,3-dioxygenase (IDO1), arginase (ARG1) and TGF-β. Adoptive transfer of T helper cells or silencing of FOXO3 by siRNAs repressed the expression of FOXO3 gene and inhibited the tolerogenicity of TADCs. Therefore, inhibition of FOXO3 signals might be a clue for improvement of cancer immunotherapy.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan. hirohash@sapmed.ac.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato