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Tolerogenic pDCs: Spotlight on Foxo3

Journal of Clinical Investigation, ISSN: 0021-9738, Vol: 121, Issue: 4, Page: 1247-1250
2011
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Article Description

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. Copyright © 2011, The American Society for Clinical Investigation.

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