Methionine enkephalin, its role in immunoregulation and cancer therapy

Int Immunopharmacol. 2016 Aug;37:59-64. doi: 10.1016/j.intimp.2016.02.015. Epub 2016 Feb 24.


Methionine enkephalin (MENK), an endogenous neuropeptide has a crucial role in both neuroendocrine and immune systems. MENK is believed to have an immunoregulatory activity to have cancer biotherapy activity by binding to the opioid receptors on immune and cancer cells. Clinical trial studies in cancer patients have shown that MENK activates immune cells directly and by inhibiting regulatory T-cells (Tregs). MENK may also change the tumor microenvironment by binding to opioid receptor on or in cancer cells. All of these mechanisms of action have biologic significance and potential for use in cancer immunotherapy. Furthermore, they reveal a relationship between the endocrine and immune systems. Due to the apparent role of MENK in cancer therapy we reviewed herein, the research undertaken with MENK in recent years; which has advanced our understanding of the role MENK has in cancer progression and its relationship to immunity, supporting MENK as a new strategy for cancer immunotherapy.

Keywords: Cancer therapy; Immunoregulation; MENK; MENKr; Methionine enkephalin; NK cells; Treg cells.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Clinical Trials as Topic
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Enkephalin, Methionine / metabolism*
  • Enkephalin, Methionine / pharmacology*
  • Humans
  • Immune System / drug effects
  • Immune System / metabolism*
  • Immunotherapy / methods*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Neurosecretory Systems / metabolism*
  • Receptors, Opioid / metabolism*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism


  • Antineoplastic Agents
  • Receptors, Opioid
  • methionine-enkephalin receptor
  • Enkephalin, Methionine