Adenosine in cancer immunotherapy: Taking off on a new plane

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Tumor immunotherapy offers durable responses but faces low response rates, necessitating novel therapeutic strategies.
• The adenosine pathway, particularly extracellular adenosine, plays a crucial role in suppressing anti-tumor immune responses within the tumor microenvironment.
• Adenosine acts on receptors like A2A on various immune cells (MDSCs, Tregs, NK cells, T cells, DCs, macrophages) to facilitate tumor immune escape.

Purpose of the Study:

• To review the role of the CD39-CD73-A2AR pathway in shaping the tumor microenvironment.
• To discuss the therapeutic targeting of the adenosinergic pathway as a strategy for cancer treatment.
• To highlight the potential of combining adenosine pathway blockade with other cancer therapies.

Main Methods:

• Review of preclinical studies on the adenosine pathway in cancer.
• Analysis of ongoing and early clinical trials targeting CD39, CD73, and A2A receptors.
• Examination of the impact of adenosine pathway inhibition on immune cells and tumor response.

Main Results:

• Preclinical data support the adenosine pathway as a novel immunotherapy checkpoint.
• Early clinical trials show antitumor efficacy of CD39, CD73, and A2A receptor inhibitors in various cancers (breast, prostate, NSCLC).
• Adenosine pathway blockade demonstrates potential to enhance responses when combined with other cancer treatments.

Conclusions:

• Targeting the CD39-CD73-A2AR pathway is a promising strategy to overcome immune suppression in the tumor microenvironment.
• Combination therapies involving adenosine pathway blockade may improve clinical outcomes for cancer patients.
• Further clinical trials are crucial to fully realize the potential of adenosinergic pathway targeting in oncology.