First Author | Gautam S | Year | 2019 |
Journal | Nat Immunol | Volume | 20 |
Issue | 3 | Pages | 337-349 |
PubMed ID | 30778251 | Mgi Jnum | J:282505 |
Mgi Id | MGI:6381090 | Doi | 10.1038/s41590-018-0311-z |
Citation | Gautam S, et al. (2019) The transcription factor c-Myb regulates CD8(+) T cell stemness and antitumor immunity. Nat Immunol 20(3):337-349 |
abstractText | Stem cells are maintained by transcriptional programs that promote self-renewal and repress differentiation. Here, we found that the transcription factor c-Myb was essential for generating and maintaining stem cells in the CD8(+) T cell memory compartment. Following viral infection, CD8(+) T cells lacking Myb underwent terminal differentiation and generated fewer stem cell-like central memory cells than did Myb-sufficient T cells. c-Myb acted both as a transcriptional activator of Tcf7 (which encodes the transcription factor Tcf1) to enhance memory development and as a repressor of Zeb2 (which encodes the transcription factor Zeb2) to hinder effector differentiation. Domain-mutagenesis experiments revealed that the transactivation domain of c-Myb was necessary for restraining differentiation, whereas its negative regulatory domain was critical for cell survival. Myb overexpression enhanced CD8(+) T cell memory formation, polyfunctionality and recall responses that promoted curative antitumor immunity after adoptive transfer. These findings identify c-Myb as a pivotal regulator of CD8(+) T cell stemness and highlight its therapeutic potential. |