CD73-adenosine: a next-generation target in immuno-oncology
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David Allard1,2, Bertrand Allard1,2, Pierre-Olivier Gaudreau1,2
1Centre de Recherche du Centre Hospitalier de l'Université de Montréal et Institut du Cancer de Montréal, Québec, Canada.
Abstract:
Cancer immunotherapy has entered in a new era with the development of first-generation immune checkpoint inhibitors targeting the PD1/PD-L1 and CTLA-4 pathways. In this context, considerable research effort is being deployed to find the next generation of cancer immunotherapeutics. The CD73-adenosine axis constitutes one of the most promising pathways in immuno-oncology. We and others have demonstrated the immunosuppressive role of CD73-adenosine in cancer and established proof-of-concept that the targeted blockade of CD73 or adenosine receptors could effectively promote anti-tumor immunity and enhance the activity of first-generation immune checkpoint blockers. With Phase I clinical trials now underway evaluating anti-CD73 or anti-A2A therapies in cancer patients, we here discuss the fundamental, preclinical and clinical findings related to the role of the CD73-adenosinergic pathway in tumor immunity.
Insights
The CD73-adenosine pathway suppresses anti-tumor immunity. Blocking this pathway, along with existing immune checkpoint inhibitors, shows promise for next-generation cancer immunotherapies in clinical trials.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Cancer immunotherapy has advanced with PD1/PD-L1 and CTLA-4 inhibitors.
- The CD73-adenosine axis is a key target for novel cancer immunotherapies.
- This pathway plays a critical immunosuppressive role in the tumor microenvironment.
Purpose of the Study:
- To review fundamental, preclinical, and clinical findings on the CD73-adenosinergic pathway in tumor immunity.
- To highlight the potential of targeting CD73 or adenosine receptors for cancer treatment.
- To discuss the combination of CD73-adenosine blockade with existing immunotherapies.
Main Methods:
- Review of existing scientific literature and clinical trial data.
- Analysis of preclinical studies demonstrating the role of CD73-adenosine in cancer.
- Examination of early-phase clinical trial results for anti-CD73 and anti-A2A therapies.
Main Results:
- The CD73-adenosine axis promotes tumor immune evasion.
- Targeting CD73 or adenosine receptors can enhance anti-tumor immune responses.
- Blocking this axis may improve the efficacy of current immune checkpoint inhibitors.
Conclusions:
- The CD73-adenosine pathway is a promising target for next-generation cancer immunotherapy.
- Clinical trials are evaluating the efficacy of targeting this pathway in cancer patients.
- Further research is needed to optimize combination strategies for maximum therapeutic benefit.
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