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The transcription factor Myb enhances CD8+ T cell stemness and antitumor immunity

ABSTRACT: Stem cells are maintained by transcriptional programs promoting self-renewal and repressing differentiation. Here, we show that the transcription factor Myb is essential for generating and maintaining stem cells within the CD8+ T-cell memory compartment. We found that, following viral infection, CD8+ T cells lacking Myb underwent terminal differentiation and exhibited impaired capacity to form CD62L+ stem cell-like memory cells. Myb acted both as a transcriptional activator of Tcf7 to enhance the development of memory cells and as a repressor of effector differentiation through Zeb2 suppression. Myb mutants’ complementation revealed that the Myb transactivation domain was necessary to restrain terminal differentiation, whereas the negative regulatory domain was critical for cell survival. Conversely, Myb overexpression enhanced CD8+ T-cell memory formation, polyfunctionality, and recall responses promoting curative antitumor immunity. These findings identify Myb as a pivotal regulator of CD8+ T-cell stemness and highlight the therapeutic potential of increasing Myb activity in CD8+ T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE112049 | GEO | 2018/11/01

REPOSITORIES: GEO

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