CD73 as a potential opportunity for cancer immunotherapy

ABSTRACT

Introduction: Cancer cells apply various mechanisms to induce and enhance immune escape. The complex network of immune-response modulating factors in the tumor microenvironment is a reason for the difficulties encountered when attempting to treat many cancers. Adenosine is a potent immune-modulating factor that can be generated through the degradation of ATP by cooperative action of NTPDase1 (CD39) and ecto-5ʹ-nucleotidase (CD73) molecules. Overexpression of CD73 on tumor and immune cells leads to the presence of a high concentration of this factor in the tumor region. Upregulation of CD73 is associated with the overproduction of adenosine; it suppresses antitumor immune responses and helps proliferation, angiogenesis, and metastasis.

Areas covered: We attempt to clarify the immunobiology of CD73 in association with its role in cancer development, angiogenesis, and metastasis. Moreover, we have reviewed CD73-targeting studies and highlighted CD73 as a potent target for cancer immunotherapy.

Expert opinion: It seems that blockade of CD73, in combination with immune checkpoint inhibitors such as anti-PD-L1 and anti-CTLA-4, can be a novel promising therapeutic strategy that can be evaluated in the future trials.

KEYWORDS:

• CD73
• cancer immunotherapy
• adenosine
• adenosine receptor

Article highlights

• Overexpression of CD73 in cancer cells leads to high levels of adenosine in the tumor site.

• Adenosine in the tumor site enhances tumor cell growth and angiogenesis and suppresses the zonal immunity.

• Suppression of CD73 can arrest tumor progression.

• Anti-CD73 mAbs and drugs in clinical trials have yielded promising results.

• Blockade of CD73 can be considered a logical anticancer therapeutic strategy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer is affiliated with, and owns stock in Surface Oncology, Cambridge, MA, USA.

Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.