title: Tolerogenic pDCs: spotlight on Foxo3.
abstract: Cancer creates a peculiar inflammatory environment enriched for transcription factors with a negative influence on adaptive immunity. In this issue of the JCI, Watkins and colleagues identify Foxo3 as a master regulator of the tolerogenic program in tumor-associated, plasmacytoid DCs (pDCs). Foxo3 enables pDCs to induce tolerance in tumor antigen-specific CD8+ T cells, turning them into regulatory lymphocytes capable of inhibiting nearby CD8+ T lymphocytes. Provision of tumor-specific CD4+ T helper cells interrupts this circuit by inhibiting Foxo3 expression and fully licensing the antigen-presenting ability of pDCs. These data identify a new target for therapeutic intervention and provide insight into the transcription factor interplay in myeloid cells recruited to the cancer microenvironment.
authors: Verona University Hospital and Department of Pathology, Immunology Section, University of Verona, Verona, Italy. vincenzo.bronte@univr.it
authors: Vincenzo
authors: V
authors: Bronte
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D051379:Mice; D018448:Models, Immunological; D011471:Prostatic Neoplasms / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse