Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment.
Nat Commun
; 13(1): 6740, 2022 11 08.
Article
en En
| MEDLINE
| ID: mdl-36347860
ABSTRACT
Single-cell sequencing technologies have noteworthily improved our understanding of the genetic map and molecular characteristics of bladder cancer (BC). Here we identify CD39 as a potential therapeutic target for BC via single-cell transcriptome analysis. In a subcutaneous tumor model and orthotopic bladder cancer model, inhibition of CD39 (CD39i) by sodium polyoxotungstate is able to limit the growth of BC and improve the overall survival of tumor-bearing mice. Via single cell RNA sequencing, we find that CD39i increase the intratumor NK cells, conventional type 1 dendritic cells (cDC1) and CD8 + T cells and decrease the Treg abundance. The antitumor effect and reprogramming of the tumor microenvironment are blockaded in both the NK cells depletion model and the cDC1-deficient Batf3-/- model. In addition, a significant synergistic effect is observed between CD39i and cisplatin, but the CD39i + anti-PD-L1 (or anti-PD1) strategy does not show any synergistic effects in the BC model. Our results confirm that CD39 is a potential target for the immune therapy of BC.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
Microambiente Tumoral
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article