CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73, a cell surface 5'nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discov...

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Bibliographic Details
Published in:Frontiers in immunology 2020-04, Vol.11, p.508-508
Main Authors: Harvey, Jerry B, Phan, Luan H, Villarreal, Oscar E, Bowser, Jessica L
Format: Article
Language:English
Subjects:
5'-Nucleotidase - metabolism
adenosine
Animals
CD73
gastrointestinal cancers
Gastrointestinal Neoplasms - immunology
Gastrointestinal Neoplasms - therapy
Humans
Immune Tolerance
Immunology
Immunomodulation
immunosuppression
immunotherapy
Immunotherapy - methods
Receptor, Adenosine A2A - metabolism
Signal Transduction
Tumor Microenvironment
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Summary:CD73, a cell surface 5'nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.00508