Immune activation is essential for the antitumor activity of EZH2 inhibition in urothelial carcinoma.
Sci Adv
; 8(40): eabo8043, 2022 10 07.
Article
em En
| MEDLINE
| ID: mdl-36197969
ABSTRACT
The long-term survival of patients with advanced urothelial carcinoma (UCa) is limited because of innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa and hypothesized that EZH2 inhibition, via a small-molecule catalytic inhibitor, might have antitumor effects in UCa. Here, in a carcinogen-induced mouse bladder cancer model, a reduction in tumor progression and an increase in immune infiltration upon EZH2 inhibition were observed. Treatment of mice with EZH2i causes an increase in MHC class II expression in the urothelium and can activate infiltrating T cells. Unexpectedly, we found that the lack of an intact adaptive immune system completely abolishes the antitumor effects induced by EZH2 catalytic inhibition. These findings show that immune evasion is the only important determinant for the efficacy of EZH2 catalytic inhibition treatment in a UCa model.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Carcinoma de Células de Transição
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article