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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Lilong Liu & Yaxin Hou & Changqi Deng & Zhen Tao & Zhaohui Chen & Junyi Hu & Ke Chen, 2022. "Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34495-z
    DOI: 10.1038/s41467-022-34495-z
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