Journal
GASTROENTEROLOGY
Volume 161, Issue 6, Pages 1813-1829Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2021.09.059
Keywords
Cyclooxygenase-2; Prostaglandin E2; Colorectal Cancer; Esophageal Cancer; Gastric Cancer; Tumor Immune Evasion; Tumor-Associated Angiogenesis; Cancer-Associated Fibroblasts
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Funding
- Hollings Cancer Center grant, Medical University of South Carolina [P30 CA138313]
- National Colorectal Cancer Research Alliance
- Alan & Kate Gibson Research Fellowship, 2018
- Department of Health and Human Services acting through the Victorian Cancer Agency, Victoria, Australia [MCRF16002]
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The cyclooxygenase-2-prostaglandin E2 pathway plays an important role in the development of gastrointestinal cancer, promoting tumor growth and affecting host defenses. Overcoming tumor immune evasion is a major challenge in cancer immunotherapy.
Chronic inflammation is a known risk factor for gastrointestinal cancer. The evidence that nonsteroidal antiinflammatory drugs suppress the incidence, growth, and metastasis of gastrointestinal cancer supports the concept that a nonsteroidal anti-inflammatory drug target, cyclooxygenase, and its downstream bioactive lipid products may provide one of the links between inflammation and cancer. Preclinical studies have demonstrated that the cyclooxygenase-2-prostaglandin E2 pathway can promote gastrointestinal cancer development. Although the role of this pathway in cancer has been investigated extensively for 2 decades, only recent studies have described its effects on host defenses against transformed epithelial cells. Overcoming tumor-immune evasion remains one of the major challenges in cancer immunotherapy. This review summarizes the impacts of the cyclooxygenase-2-prostaglandin E2 pathway on gastrointestinal cancer development. Our focus was to highlight recent advances in our understanding of how this pathway induces tumor immune evasion.
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