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Influence of opioids on immune function in patients with cancer pain: from bench to bedside

Boland, Jason W; Pockley, A Graham


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Dr Jason Boland
Senior Clinical Lecturer and Honorary Consultant in Palliative Medicine

A Graham Pockley


In patients with cancer, opioids are principally used for the management of acute surgical and chronic cancer-related pain. However, opioids have many non-analgesic effects, including direct and indirect effects on cancer cells and on anti-tumour immunity (natural killer (NK) cells, macrophages and T-cells). Direct effects on immune cells are manifested via opioid and non-opioid Toll-like receptors, whereas indirect effects are manifested via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Opioids can also decrease/alter immune cell infiltration into the tumour microenvironment. Animal models have shown that this is not a class effect, in that morphine and fentanyl suppress NK cell cytotoxicity; buprenorphine does not affect NK cell cytotoxicity, whereas tramadol increases NK cell cytotoxicity, reducing metastasis. In healthy individuals, morphine suppresses and fentanyl enhances NK cell cytotoxicity. In patients undergoing surgery, fentanyl decreased and tramadol increased NK cell cytotoxicity; clinical outcomes were not determined. Meta-analyses of opioid-sparing surgical studies report an association between improved recurrence-free and/or overall survival with regional/neuraxial anaesthesia compared with systemic opioids. In patients receiving opioids for non-surgical cancer-related pain, morphine has variable effects on immunity; clinical outcomes were not assessed. Although there is a potential association between systemic opioid administration s and shorter survival in cancer patients with a prognosis of months to years, studies have not been designed to primarily assess survival, as a consequence of which causality cannot be apportioned. Pain is immunosuppressive, so analgesia is important. Opioids for cancer-related pain will continue to be recommended until definitive data on the effects of opioids on clinical outcomes in specific patient groups becomes available.


Boland, J. W., & Pockley, A. G. (in press). Influence of opioids on immune function in patients with cancer pain: from bench to bedside. British Journal of Pharmacology, 175(14), 2726-2736.

Journal Article Type Article
Acceptance Date May 30, 2017
Online Publication Date Jul 9, 2017
Deposit Date May 31, 2017
Publicly Available Date Jun 12, 2018
Journal British journal of pharmacology
Print ISSN 0007-1188
Electronic ISSN 1476-5381
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 175
Issue 14
Pages 2726-2736
Keywords Opioids; Immunity; Cancer; Pain; Natural killer (NK) cells; Survival; Surgery
Public URL
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Additional Information This is a description of an article accepted for future publication in: British journal of pharmacology, 2017.


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