Proceedings of the National Academy of Sciences · 2017 · 48 citations · 55 references
Life SciencesImmunologyOncologyCancer ImmunologyInnate ImmunityTumor ImmunologyCancer ImmunotherapyCheckpoint Inhibitor TherapyCytokine BiologyImmune Checkpoint InhibitorsInflammatory SignalingTumor Immune MicroenvironmentAnticancer ActivityAntitumor Cytokine ResponsesAntitumor Immune ActivationCancer-associated MacrophagesCytokine Signaling In CancerInnate Antitumor ImmunityToll-like Receptor SignalingTumor-associated Cytokines
Significance The therapeutic activity of checkpoint blockers and toll-like receptor (TLR) agonists, which show some efficacy against malignancies, appears to at least partially result from the secretion of type-I IFNs. Thus, we hypothesized that type-I IFN-inducible transcription factors, such as basic leucine zipper transcription factor ATF-like 2 ( Batf2 ), might play a role in tumor immunity. Here, we investigated the role of Batf2 , especially its positive transcriptional activities, and evaluated its antitumor effect. This study shows that Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces the activation of CD8 + T cells and their accumulation within the tumor. Batf2 may be an important target in anticancer treatment with immune checkpoint blockers and TLR agonists.
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