The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity.
Nat Immunol
; 20(3): 337-349, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30778251
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
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Linfocitos T CD8-positivos
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Proteínas Proto-Oncogénicas c-myb
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Memoria Inmunológica
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Neoplasias Experimentales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article