First Author | Liu L | Year | 2022 |
Journal | Nat Commun | Volume | 13 |
Issue | 1 | Pages | 6740 |
PubMed ID | 36347860 | Mgi Jnum | J:347087 |
Mgi Id | MGI:7386259 | Doi | 10.1038/s41467-022-34495-z |
Citation | Liu L, et al. (2022) Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment. Nat Commun 13(1):6740 |
abstractText | 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. |