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Publication : Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment.

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.
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