Histone deacetylase inhibition promotes intratumoral CD8+ T-cell responses, sensitizing murine breast tumors to anti-PD1.
Cancer Immunol Immunother
; 68(12): 2081-2094, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31720815
ABSTRACT
Histone deacetylase (HDAC) inhibitors impair tumor cell proliferation and alter gene expression. However, the impact of these changes on anti-tumor immunity is poorly understood. Here, we showed that the class I HDAC inhibitor, entinostat (ENT), promoted the expression of immune-modulatory molecules, including MHCII, costimulatory ligands, and chemokines on murine breast tumor cells in vitro and in vivo. ENT also impaired tumor growth in vivo-an effect that was dependent on both CD8+ T cells and IFNγ. Moreover, ENT promoted intratumoral T-cell clonal expansion and enhanced their functional activity. Importantly, ENT sensitized normally unresponsive tumors to the effects of PD1 blockade, predominantly through increases in T-cell proliferation. Our findings suggest that class I HDAC inhibitors impair tumor growth by enhancing the proliferative and functional capacity of CD8+ T cells and by sensitizing tumor cells to T-cell recognition.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Benzamidas
/
Neoplasias de la Mama
/
Linfocitos Infiltrantes de Tumor
/
Linfocitos T CD8-positivos
/
Resistencia a Antineoplásicos
/
Inhibidores de Histona Desacetilasas
/
Anticuerpos Monoclonales
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Immunol Immunother
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos