The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors

Front Immunol. 2022 Jan 6:12:802049. doi: 10.3389/fimmu.2021.802049. eCollection 2021.

Abstract

Tumor immunotherapy, one of the efficient therapies in cancers, has been called to the scientific community's increasing attention lately. Among them, immune checkpoint inhibitors, providing entirely new modalities to treat cancer by leveraging the patient's immune system. They are first-line treatments for varieties of advanced malignancy, such as melanoma, gastrointestinal tumor, esophageal cancer. Although immune checkpoint inhibitors (ICIs) treatment has been successful in different cancers, drug resistance and relapses are common, such as in colorectal cancer. Therefore, it is necessary to improve the efficacy of immune checkpoint therapy for cancer patients who do not respond or lowly response to current treatments. N6-methyladenosine (m6A), as a critical regulator of transcript expression, is the most frequently internal modification of mRNA in the human body. Recently, it has been proposed that m6A epigenetic modification is a potential driver of tumor drug resistance. In this report, we will briefly outline the relevant mechanisms, general treatment status of immune checkpoint inhibitors in colorectal cancer, how m6A epigenetic modifications regulate the response of ICIs in CRC and provide new strategies for overcoming the resistance of ICIs in CRC.

Keywords: ICB; colorectal cancer; m6A epigenetics; overcome resistance; resistance.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Adenosine / analogs & derivatives*
  • Animals
  • Biomarkers, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Management
  • Disease Susceptibility
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / metabolism
  • Immunity, Innate / drug effects
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Immune Checkpoint Proteins
  • N-methyladenosine
  • Adenosine