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

• Published in: Nature communications 2022-11, Vol.13 (1), p.6740-6740, Article 6740
• Main Authors: Liu, Lilong, Hou, Yaxin, Deng, Changqi, Tao, Zhen, Chen, Zhaohui, Hu, Junyi, Chen, Ke
• Format: Article
• Language: English
• Subjects: 13/105; 13/31; 13/51; 38/1; 38/91; 631/250/580; 631/67/580; 631/67/589/1336; 64/60; Animals; Anticancer properties; Antitumor activity; Bladder; Bladder cancer; Cancer; CD8 antigen; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cisplatin; Dendritic Cells; Depletion; Gene sequencing; Heterogeneity; Humanities and Social Sciences; Immunotherapy; Killer Cells, Natural; Lymphocytes; Lymphocytes T; Mice; Molecular modelling; multidisciplinary; PD-1 protein; PD-L1 protein; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Synergistic effect; Therapeutic targets; Transcriptomes; Tumor Microenvironment; Tumors; Urinary Bladder Neoplasms - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34495-z

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. The molecular mechanisms underlying tumour heterogeneity in bladder cancer remain to be explored. Here, the authors perform single cell RNA sequencing and identify CD39 as a potential target for immunotherapy, which they validate in vivo.