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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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    1. Sanjeev Mariathasan & Shannon J. Turley & Dorothee Nickles & Alessandra Castiglioni & Kobe Yuen & Yulei Wang & Edward E. Kadel III & Hartmut Koeppen & Jillian L. Astarita & Rafael Cubas & Suchit Jhunj, 2018. "TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells," Nature, Nature, vol. 554(7693), pages 544-548, February.
    2. Barbara Maier & Andrew M. Leader & Steven T. Chen & Navpreet Tung & Christie Chang & Jessica LeBerichel & Aleksey Chudnovskiy & Shrisha Maskey & Laura Walker & John P. Finnigan & Margaret E. Kirkling , 2020. "Author Correction: A conserved dendritic-cell regulatory program limits antitumour immunity," Nature, Nature, vol. 582(7813), pages 17-17, June.
    3. Lei Zhang & Xin Yu & Liangtao Zheng & Yuanyuan Zhang & Yansen Li & Qiao Fang & Ranran Gao & Boxi Kang & Qiming Zhang & Julie Y. Huang & Hiroyasu Konno & Xinyi Guo & Yingjiang Ye & Songyuan Gao & Shan , 2018. "Lineage tracking reveals dynamic relationships of T cells in colorectal cancer," Nature, Nature, vol. 564(7735), pages 268-272, December.
    4. Xu Wang & Jonathan Wilhelm & Wei Li & Suxin Li & Zhaohui Wang & Gang Huang & Jian Wang & Houliang Tang & Sina Khorsandi & Zhichen Sun & Bret Evers & Jinming Gao, 2020. "Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    5. Barbara Maier & Andrew M. Leader & Steven T. Chen & Navpreet Tung & Christie Chang & Jessica LeBerichel & Aleksey Chudnovskiy & Shrisha Maskey & Laura Walker & John P. Finnigan & Margaret E. Kirkling , 2020. "A conserved dendritic-cell regulatory program limits antitumour immunity," Nature, Nature, vol. 580(7802), pages 257-262, April.
    6. Roser Vento-Tormo & Mirjana Efremova & Rachel A. Botting & Margherita Y. Turco & Miquel Vento-Tormo & Kerstin B. Meyer & Jong-Eun Park & Emily Stephenson & Krzysztof Polański & Angela Goncalves & Lucy, 2018. "Single-cell reconstruction of the early maternal–fetal interface in humans," Nature, Nature, vol. 563(7731), pages 347-353, November.
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