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

Lilong Liu, Yaxin Hou, Changqi Deng, Zhen Tao (), Zhaohui Chen (), Junyi Hu () and Ke Chen ()
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Lilong Liu: Huazhong University of Science and Technology
Yaxin Hou: Huazhong University of Science and Technology
Changqi Deng: Huazhong University of Science and Technology
Zhen Tao: Tianjin Medical University Cancer institute & Hospital
Zhaohui Chen: Huazhong University of Science and Technology
Junyi Hu: Huazhong University of Science and Technology
Ke Chen: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34495-z

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