Mij
Senior Member (Voting Rights)
Significance
CD8+ T cell dysfunction limits immune control in cancer and chronic viral infections. Here, we define extracellular adenosine as a critical metabolic driver of dysfunction and a context-integrating checkpoint, synthesizing insights across disease settings to inform improved therapeutic targeting.
Highlights
-Adenosine functions as a context-integrating metabolic checkpoint that constrains CD8+ T cell activity.
-Distinct drivers in cancer and chronic infection induce a shared state of dysfunction in CD8+ T cells.
-Adenosine signaling reinforces checkpoint pathways and stabilizes dysfunctional T cell states.
-Therapeutic targeting of the adenosine axis requires combination and context-specific strategies.
Abstract
CD8+ T cell dysfunction, characterized by impaired effector function, proliferative capacity, and sustained inhibitory receptor expression, limits immune control in both cancer and chronic viral infections. Despite arising from distinct disease processes, these conditions induce a shared state of CD8+ T cell dysfunction, suggesting convergence on common regulatory pathways.
Adenosine (ADO), an immunosuppressive purine metabolite generated through extracellular ATP catabolism, has emerged as a context-integrating metabolic checkpoint that regulates immune responses in response to tissue stress and inflammation. Across tumors and HIV, dysregulated ADO signaling reinforces checkpoint pathways and stabilizes dysfunctional CD8+ T cell states.
In this review, we examine how the ADO–adenosine deaminase-1 axis shapes CD8+ T cell dysfunction across disease contexts and discuss its potential as a broadly applicable target for immune restoration.
STUDY
CD8+ T cell dysfunction limits immune control in cancer and chronic viral infections. Here, we define extracellular adenosine as a critical metabolic driver of dysfunction and a context-integrating checkpoint, synthesizing insights across disease settings to inform improved therapeutic targeting.
Highlights
-Adenosine functions as a context-integrating metabolic checkpoint that constrains CD8+ T cell activity.
-Distinct drivers in cancer and chronic infection induce a shared state of dysfunction in CD8+ T cells.
-Adenosine signaling reinforces checkpoint pathways and stabilizes dysfunctional T cell states.
-Therapeutic targeting of the adenosine axis requires combination and context-specific strategies.
Abstract
CD8+ T cell dysfunction, characterized by impaired effector function, proliferative capacity, and sustained inhibitory receptor expression, limits immune control in both cancer and chronic viral infections. Despite arising from distinct disease processes, these conditions induce a shared state of CD8+ T cell dysfunction, suggesting convergence on common regulatory pathways.
Adenosine (ADO), an immunosuppressive purine metabolite generated through extracellular ATP catabolism, has emerged as a context-integrating metabolic checkpoint that regulates immune responses in response to tissue stress and inflammation. Across tumors and HIV, dysregulated ADO signaling reinforces checkpoint pathways and stabilizes dysfunctional CD8+ T cell states.
In this review, we examine how the ADO–adenosine deaminase-1 axis shapes CD8+ T cell dysfunction across disease contexts and discuss its potential as a broadly applicable target for immune restoration.
STUDY