The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies

Area of Science:

• Immunology
• Cancer Biology
• Pharmacology

Background:

• Adenosine (Ado) levels are elevated in the tumor microenvironment (TME).
• Adenosine binds to adenosine receptors (AdoRs), suppressing adaptive anti-tumor immunity.
• This suppression involves multiple mechanisms impacting immune cells and their functions.

Purpose of the Study:

• To summarize and analyze the inhibitory effects of adenosine on tumor adaptive immunity.
• To elucidate the molecular mechanisms underlying adenosine's immunosuppression.
• To provide an overview of therapeutic strategies targeting adenosine pathways in cancer.

Main Methods:

• Review of preclinical and clinical studies on adenosine's role in tumor immunity.
• Analysis of molecular pathways affected by adenosine, including MHC II, co-stimulatory factors, cytokines, and immune checkpoints.
• Examination of adenosine's impact on dendritic cells, macrophages, and T cells.

Main Results:

• Adenosine downregulates MHC II and co-stimulatory factors on antigen-presenting cells, impairing antigen presentation.
• Adenosine inhibits T cell receptor signaling, anti-tumor cytokine secretion, and effector T cell infiltration.
• Adenosine diminishes T cell cytotoxicity by promoting immunosuppressive factors and enhancing immune checkpoint activity.

Conclusions:

• Reducing adenosine production or blocking AdoRs can enhance anti-tumor immune responses.
• Targeting adenosine pathways represents a promising strategy to improve cancer immunotherapy efficacy.
• Further development of inhibitors targeting adenosine generation or AdoRs is crucial for clinical application.