Methionine-Enkephalin Modulation in Cancer Immunotherapy
Summary
Methionine-enkephalin, also known as the opioid growth factor (OGF), is a naturally occurring pentapeptide that exerts tonic inhibition on cell proliferation through its receptor (OGFr). In cancer immunotherapy contexts, this axis has been revisited not only for its direct antiproliferative effects but also for its capacity to modulate innate and adaptive immune responses within the tumour microenvironment. By engaging OGFr, OGF induces cell-cycle arrest in the G0/G1 phase via upregulation of cyclin-dependent kinase inhibitors such as p21, thereby slowing tumour growth. Concurrently, methionine-enkephalin can act on myeloid cells to promote pro-inflammatory phenotypes, enhance phagocytic function and potentiate antitumour immunity. The duality of direct tumour suppression and immune modulation positions methionine-enkephalin as a promising adjunct to existing checkpoint inhibitors and adoptive-cell therapies. Ongoing research explores dosing regimens, delivery platforms and combination strategies to harness this endogenous peptide’s full therapeutic potential while minimising off-target effects.
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Methionine-Enkephalin Modulation in Cancer Immunotherapy publication trend
The graph below shows the total number of articles in methionine-enkephalin modulation in cancer immunotherapy across all publications each year (not limited to Nature Index journals).
Technical terms
Methionine-enkephalin (OGF): An endogenous opioid pentapeptide that binds specifically to OGFr to regulate cell proliferation and immune function.
Opioid growth factor receptor (OGFr): A non-classical opioid receptor that mediates the growth-inhibitory effects of methionine-enkephalin through nuclear localisation and interaction with cell-cycle regulators.
Cyclin-dependent kinase inhibitor p21: A protein that binds to and inhibits cyclin-CDK complexes, enforcing G0/G1 cell-cycle arrest in response to OGF signalling.
Macrophage polarization: The process by which macrophages adopt distinct functional phenotypes—such as pro-inflammatory (M1) or anti-inflammatory (M2)—in response to microenvironmental cues, including opioid peptides.
G0/G1 cell-cycle arrest: A checkpoint in the early cell-cycle phases where cells exit proliferation temporarily, often induced by growth-regulatory signals like methionine-enkephalin.
References
- The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer. Molecular Cancer (2008).
- Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis. BMC Cancer (2009).
- Overexpression of OGFr Downregulates Ovarian Cancer Cell Proliferation In Vitro and Inhibits Tumorigenesis. Journal of Cancer Therapy (2011).
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