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CD73-generated adenosine: orchestrating the tumor-stroma interplay to promote cancer growth
Bertrand Allard1, Martin Turcotte, John Stagg
1Centre de Recherche, Centre Hospitalier, Faculté de Pharmacie l'Université de Montréal et Institut du Cancer de Montréal, Montréal, QC H2L 4M1, Canada.
Abstract:
Despite the coming of age of cancer immunotherapy, clinical benefits are still modest. An important barrier to successful cancer immunotherapy is that tumors employ a number of mechanisms to facilitate immune escape, including the production of anti-inflammatory cytokines, the recruitment of regulatory immune subsets, and the production of immunosuppressive metabolites. Significant therapeutic opportunity exists in targeting these immunosuppressive pathways. One such immunosuppressive pathway is the production of extracellular adenosine by CD73, an ectonucleotidase overexpressed in various types of cancer. We hereafter review the biology of CD73 and its role in cancer progression and metastasis. We describe the role of extracellular adenosine in promoting tumor growth through paracrine and autocrine action on tumor cells, endothelial cells, and immune cells.
Insights
Cancer immunotherapy faces challenges due to tumor immune escape. Targeting CD73 (an ectonucleotidase) and its production of adenosine offers a promising therapeutic strategy to overcome this barrier.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Cancer immunotherapy has advanced, but clinical benefits remain limited.
- Tumors utilize immune escape mechanisms, including immunosuppressive cytokines and metabolites.
- Extracellular adenosine, produced by CD73, is a key immunosuppressive factor in the tumor microenvironment.
Purpose of the Study:
- To review the biology of CD73 (an ectonucleotidase).
- To elucidate the role of CD73 and extracellular adenosine in cancer progression and metastasis.
- To highlight therapeutic opportunities in targeting the CD73/adenosine pathway.
Main Methods:
- Literature review of CD73 biology.
- Analysis of CD73's role in tumor immune evasion.
- Examination of adenosine's effects on tumor and immune cells.
Main Results:
- CD73 is overexpressed in various cancers, contributing to immune suppression.
- Extracellular adenosine promotes tumor growth via paracrine and autocrine signaling.
- Adenosine impacts tumor cells, endothelial cells, and immune cells, fostering an immunosuppressive environment.
Conclusions:
- Targeting CD73 and its adenosine production is a viable strategy to enhance cancer immunotherapy.
- Understanding the CD73/adenosine axis is crucial for developing novel anti-cancer therapies.
- Inhibiting CD73 may reverse tumor-induced immunosuppression and improve treatment outcomes.
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