Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer

Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.

Abstract

Chronic inflammation is a known risk factor for gastrointestinal cancer. The evidence that nonsteroidal anti-inflammatory 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.

Trial registration: ClinicalTrials.gov NCT04344795 NCT03026140 NCT03926338 NCT03658772.

Keywords: Cancer-Associated Fibroblasts; Colorectal Cancer; Cyclooxygenase-2; Esophageal Cancer; Gastric Cancer; Prostaglandin E2; Tumor Immune Evasion; Tumor-Associated Angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cancer-Associated Fibroblasts / enzymology
  • Cancer-Associated Fibroblasts / immunology
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Dinoprostone / metabolism*
  • Epithelial Cells / enzymology
  • Epithelial Cells / immunology
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / enzymology*
  • Gastrointestinal Neoplasms / immunology
  • Gastrointestinal Neoplasms / pathology
  • Humans
  • Immunotherapy
  • Inflammation Mediators / metabolism*
  • Lymphocytes, Tumor-Infiltrating / enzymology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Signal Transduction
  • Tumor Escape* / drug effects
  • Tumor Microenvironment / immunology*
  • Tumor-Associated Macrophages / enzymology
  • Tumor-Associated Macrophages / immunology

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Inflammation Mediators
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone

Associated data

  • ClinicalTrials.gov/NCT04344795
  • ClinicalTrials.gov/NCT03026140
  • ClinicalTrials.gov/NCT03926338
  • ClinicalTrials.gov/NCT03658772