Research ArticleCancer Immunology

Bypassing STAT3-mediated inhibition of the transcriptional regulator ID2 improves the antitumor efficacy of dendritic cells

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Science Signaling  27 Sep 2016:
Vol. 9, Issue 447, pp. ra94
DOI: 10.1126/scisignal.aaf3957

Engineering antitumor activity

Dendritic cells are critical mediators of the immune response to infection. Despite their potential, antitumor vaccines based on injecting dendritic cells have not been effective. Using mouse models of melanoma, Li et al. found that tumor cells release cytokines that suppress the ability of tumor-infiltrating dendritic cells to mount an antitumor response. The cytokines released from melanoma cells activated the transcription factor STAT3, which repressed the expression of the gene encoding the transcription regulator ID2. Constitutively expressing ID2 dampened production of proinflammatory cytokines in dendritic cells and promoted dendritic cell–mediated immunostimulatory lymphocyte responses. Vaccination experiments in tumor-bearing mice suggested that engineering dendritic cells to overcome or prevent the tumor-derived cytokine response in the injected dendritic cells, by either deleting STAT3 or overexpressing ID2, might prove an effective immunotherapy strategy in cancer patients.

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