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; Ke Chen

doi:10.1038/s41467-022-34495-z

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

Nat Commun. 2022 Nov 8;13(1):6740. doi: 10.1038/s41467-022-34495-z.

Authors

Lilong Liu^#¹, Yaxin Hou^#², Changqi Deng¹, Zhen Tao³, Zhaohui Chen⁴, Junyi Hu⁵, Ke Chen⁶

Affiliations

¹ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Radiation Oncology and Cyberknife Center, Tianjin Medical University Cancer institute & Hospital, Tianjin, China. ztao@tmu.edu.cn.
⁴ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. zhaohuichen@hust.edu.cn.
⁵ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 531572782@qq.com.
⁶ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. shenke@hust.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Dendritic Cells
Killer Cells, Natural
Mice
Tumor Microenvironment*
Urinary Bladder Neoplasms* / metabolism