Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK).

Abstract

The aim of this study was to investigate the immunological mechanisms by which synthetic methionine enkephalin (MENK) exerts therapeutic effects on tumor growth. Our findings in vivo or in vitro show that MENK treatment either in vivo or in vitro could up-regulate the percentages of CD8+T cells, induce markers of activated T cells, increased cytotoxic activity against mouse S180 tumor cells and increase secretion of IFNγ. In addition, the adoptively transferred CD8+T cells, after either in vitro or in vivo treatment with MENK, result in significantly increased survival of S180 tumor-bearing mice and significant shrinkage in tumor growth. Opioid receptors are detected on normal CD8+T cells and exposure to MENK leads to increased expression of opioid receptors. Interaction between MENK and the opioid receptors on CD8+T cells appears to be essential for the activation of CTL, since the addition of naltrexone (NTX), an opioid receptor antagonist, significantly inhibits all of the effects of MENK. The evidence obtained indicates that the MENK-induced T cell signaling is associated with a significant up-regulation of Ca2+ influx into the cytoplasm and the translocation of NFAT2 into nucleus, and these signaling effects are also inhibited by naltrexone.

• Authors: Weiwei Li, Wenna Chen, Ronald B Herberman, Nicolas P Plotnikoff, Gene Youkilis, Noreen Griffin, Enhua Wang, Changlong Lu, Fengping Shan
• Journal: Cancer letters (Cancer Lett) Vol. 344 Issue 2 Pg. 212-22 (Mar 28 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 24291668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Receptors, Opioid, delta
• Receptors, Opioid, mu
• Enkephalin, Methionine
• Calcium

Topics

• Animals
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Calcium (metabolism)
• Cell Nucleus (immunology, metabolism)
• Enkephalin, Methionine (immunology, pharmacology)
• Immunotherapy, Adoptive (methods)
• Lymphocyte Activation (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Random Allocation
• Receptors, Opioid, delta (biosynthesis, immunology)
• Receptors, Opioid, mu (biosynthesis, immunology)
• Sarcoma 180 (drug therapy, immunology, therapy)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)