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

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 orthotopi...

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Autores principales: Liu, Lilong, Hou, Yaxin, Deng, Changqi, Tao, Zhen, Chen, Zhaohui, Hu, Junyi, Chen, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643495/
https://www.ncbi.nlm.nih.gov/pubmed/36347860
http://dx.doi.org/10.1038/s41467-022-34495-z
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author Liu, Lilong
Hou, Yaxin
Deng, Changqi
Tao, Zhen
Chen, Zhaohui
Hu, Junyi
Chen, Ke
author_facet Liu, Lilong
Hou, Yaxin
Deng, Changqi
Tao, Zhen
Chen, Zhaohui
Hu, Junyi
Chen, Ke
author_sort Liu, Lilong
collection PubMed
description 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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spelling pubmed-96434952022-11-15 Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment Liu, Lilong Hou, Yaxin Deng, Changqi Tao, Zhen Chen, Zhaohui Hu, Junyi Chen, Ke Nat Commun Article 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. Nature Publishing Group UK 2022-11-08 /pmc/articles/PMC9643495/ /pubmed/36347860 http://dx.doi.org/10.1038/s41467-022-34495-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Lilong
Hou, Yaxin
Deng, Changqi
Tao, Zhen
Chen, Zhaohui
Hu, Junyi
Chen, Ke
Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment
title Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment
title_full Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment
title_fullStr Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment
title_full_unstemmed Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment
title_short Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment
title_sort single cell sequencing reveals that cd39 inhibition mediates changes to the tumor microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643495/
https://www.ncbi.nlm.nih.gov/pubmed/36347860
http://dx.doi.org/10.1038/s41467-022-34495-z
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