IRF4 instructs effector Treg differentiation and immune suppression in human cancer.
J Clin Invest
; 130(6): 3137-3150, 2020 06 01.
Article
en En
| MEDLINE
| ID: mdl-32125291
ABSTRACT
The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Linfocitos T Reguladores
/
Factores Reguladores del Interferón
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Microambiente Tumoral
/
Proteínas de Neoplasias
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Aged80
/
Animals
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Invest
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia