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Cyclooxygenase-2 Inhibitor: A Potential Combination Strategy With Immunotherapy in Cancer

Dan Pu1, Liyuan Yin1, Lin Huang1

  • 1Department of Lung Cancer Center, Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Frontiers in Oncology
|March 15, 2021
PubMed

Insights

Cyclooxygenase-2 (COX-2) promotes tumor growth and immune evasion. Inhibiting COX-2 may improve immunotherapy response by reducing prostaglandin E2 (PGE2) immunosuppression in the tumor microenvironment.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Immunotherapy has revolutionized cancer treatment but faces challenges with patient response.
  • Cyclooxygenase-2 (COX-2) is upregulated in many cancers, correlating with poor prognosis.
  • Prostaglandin E2 (PGE2), produced by COX-2, fuels tumor progression and metastasis.

Purpose of the Study:

  • To elucidate the role of the COX-2/PGE2 pathway in creating an immunosuppressive tumor microenvironment (TME).
  • To review how PGE2 contributes to immune evasion and hinders immunotherapy efficacy.
  • To summarize the therapeutic potential of COX-2 inhibitors in combination with immune checkpoint inhibitors (ICIs).

Main Methods:

  • Review of preclinical and clinical studies on COX-2, PGE2, and cancer immunology.
  • Analysis of mechanisms by which PGE2 mediates immunosuppression within the TME.
  • Examination of clinical trials investigating COX-2 inhibitors and ICIs.

Main Results:

  • PGE2 actively suppresses anti-tumor immunity through various mechanisms within the TME.
  • Elevated COX-2/PGE2 signaling is linked to resistance to current immunotherapies.
  • COX-2 inhibitors show promise in counteracting PGE2-induced immunosuppression.

Conclusions:

  • The COX-2/PGE2 axis is a critical regulator of the immunosuppressive TME.
  • Targeting COX-2 may overcome immunotherapy resistance and enhance treatment outcomes.
  • Further clinical investigation of COX-2 inhibitors with ICIs is warranted for improved cancer therapy.
Keywords:
cancercelecoxibcombination therapycyclooxygenase-2immunotherapy

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