CD39/CD73-mediated immunosuppression and tumor aggressiveness in bladder cancer

Area of Science:

• Immunology
• Oncology
• Cancer Research

Background:

• Urothelial bladder cancer (BCa) has high recurrence and mortality rates, with limited immunotherapy efficacy due to immune evasion.
• The adenosinergic pathway (AP), mediated by CD39 and CD73, is a known immunosuppressive mechanism, but its role in BCa is not well understood.

Purpose of the Study:

• To investigate the role of the adenosinergic pathway (AP) in bladder cancer (BCa) immunosuppression.
• To analyze the immunophenotypic characteristics of peripheral blood (PB) and tumor microenvironment (TME) in BCa patients.
• To identify potential non-invasive biomarkers for assessing tumor infiltration and grade.

Main Methods:

• Integrated immunophenotypic analysis using multicolor flow cytometry and immunohistochemistry.
• Analysis of peripheral blood (PB) and tumor microenvironment (TME) samples from 39 BCa patients and 14 healthy controls.
• Assessment of CD39 and CD73 expression on T cells and correlation with immune cell populations and tumor characteristics.

Main Results:

• High-risk (HR) BCa patients showed systemic immunosuppression, including increased regulatory T cells (Tregs) and decreased cytotoxic T cells.
• CD39 and CD73 expression on T cells correlated with an immunosuppressive TME, characterized by M2-like macrophages and reduced effector T cells.
• Circulating CD39+/CD73+ T cells mirrored intratumoral composition, with specific subsets associated with higher pathological grade and tumor infiltration.

Conclusions:

• Bladder cancer (BCa) exhibits significant adenosinergic pathway (AP)-mediated immunosuppression.
• Specific circulating T cell subsets expressing CD39 and CD73 may serve as non-invasive biomarkers for BCa.
• These biomarkers show potential for assessing tumor infiltration and pathological grade in BCa patients.