Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
Immunotherapy. 2011 Aug;3(8):945-7. doi: 10.2217/imt.11.94.
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.
沃特金斯 SK、朱 Z、里博尔迪 E 等人。FOXO3 程序肿瘤相关树突状细胞在人类和鼠前列腺癌中成为耐受性。临床投资。121(4)，1361-1372(2011)。肿瘤相关树突状细胞（TADCs）在癌症中被描述为免疫抑制细胞，部分分子机制已经出现。转录因子 FOXO3——肿瘤抑制剂之一——在浸润人类前列腺癌和 TRAMP 前列腺癌小鼠模型中的 TADCs 中过度表达，并诱导包括吲哚胺 2,3-双加氧酶（IDO1）、精氨酸酶（ARG1）和 TGF-β在内的免疫抑制基因的表达。辅助性 T 细胞的过继转移或 siRNAs 沉默 FOXO3 抑制了 FOXO3 基因的表达并抑制了 TADCs 的耐受性。因此，抑制 FOXO3 信号可能是改善癌症免疫治疗的线索。
