2. Academic Validation
  3. Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment

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.
Lilong Liu # 1,  Yaxin Hou # 2,  Changqi Deng 1,  Zhen Tao 3,  Zhaohui Chen 4,  Junyi Hu 5,  Ke Chen 6
Affiliations

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. [email protected].
  • 4 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 5 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 6 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • # Contributed equally.
PMID: 36347860 DOI: 10.1038/s41467-022-34495-z
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.

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