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

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Single-cell sequencing advances understanding of bladder cancer (BC) genetics and molecular profiles.
• Identifying novel therapeutic targets is crucial for improving BC treatment outcomes.

Purpose of the Study:

• To investigate CD39 as a potential therapeutic target for bladder cancer using single-cell transcriptome analysis.
• To evaluate the efficacy of CD39 inhibition (CD39i) in preclinical BC models.

Main Methods:

• Single-cell RNA sequencing was employed to analyze tumor immune microenvironments.
• Preclinical models, including subcutaneous and orthotopic bladder cancer models, were used.
• CD39 inhibition was achieved using sodium polyoxotungstate.

Main Results:

• CD39 inhibition limited BC growth and improved survival in mouse models.
• CD39i increased intratumor natural killer (NK) cells, CD8+ T cells, and conventional type 1 dendritic cells (cDC1), while decreasing regulatory T cells (Tregs).
• Antitumor effects were dependent on NK cells and cDC1s; synergistic effects were observed with cisplatin, but not with anti-PD-L1/PD-1 therapies.

Conclusions:

• CD39 is a viable therapeutic target for bladder cancer immunotherapy.
• Modulating the tumor immune microenvironment via CD39 inhibition holds promise for BC treatment.
• Combination therapy with CD39i and cisplatin may offer a synergistic approach for BC management.