{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:22:57Z","timestamp":1790508177027,"version":"4.1.0"},"reference-count":13,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006398","name":"Roswell Park Alliance Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006398","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,5,3]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>\n                    Opioids remain a mainstay for managing moderate-to-severe cancer pain, yet accumulating evidence suggests that opioid analgesics can impair antitumor immunity. In their recent study, McIlvried\n                    <jats:italic>et al<\/jats:italic>\n                    propose a mechanistic framework for how morphine administration compromises response to anti-programmed-death-1 immunotherapy in a syngeneic mouse model of oral squamous cell carcinoma. They identify mu-opioid receptor signaling on CD8+ T cells as the main conduit for morphine-induced immunosuppression, observing reduced T-cell infiltration, enhanced expression of inhibitory receptors, and diminished tumor control when morphine is used. Remarkably, these adverse effects are reversed by peripherally acting mu-opioid receptor antagonists (PAMORAs), which block immunosuppression in the tumor microenvironment while presumably preserving central pain relief. Their work highlights a critical intersection between opioid-based analgesia and immunotherapy, emphasizing the need for clinicians and researchers to weigh pain control approaches against potential immunologic consequences. This commentary explores the study\u2019s implications for head and neck cancer management, addresses practical ways to mitigate opioid-induced immune inhibition, and calls for prospective trials incorporating PAMORAs in immuno-oncology protocols. Balancing effective analgesia with optimal tumor-directed immunity may yield better outcomes for patients with oral cancer and beyond.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-011644","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:16:21Z","timestamp":1747718181000},"page":"e011644","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Mending the divide: integrating opioid analgesia and immunotherapy for optimal cancer care"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-5847","authenticated-orcid":false,"given":"Celia","family":"DeJohn","sequence":"first","affiliation":[{"name":"Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0142-7375","authenticated-orcid":false,"given":"Emese","family":"Zsiros","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"2025100302441448000_13.5.e011644.1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-009962","article-title":"Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma","volume":"12","author":"McIlvried","year":"2024","journal-title":"Journal for ImmunoTherapy of Cancer 2024"},{"key":"2025100302441448000_13.5.e011644.2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.jss.2016.02.031","article-title":"Morphine and ketamine inhibit immune function of gastric cancer patients by increasing percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in vitro","volume":"203","author":"Hou","year":"2016","journal-title":"J Surg Res"},{"key":"2025100302441448000_13.5.e011644.3","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116665","article-title":"Effects of opioid drugs on immune function in cancer patients","volume":"175","author":"Li","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"2025100302441448000_13.5.e011644.4","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.9"},{"key":"2025100302441448000_13.5.e011644.5","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/mi.2016.9","article-title":"Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation","volume":"9","author":"Banerjee","year":"2016","journal-title":"Mucosal Immunol"},{"key":"2025100302441448000_13.5.e011644.6","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1007\/s10637-020-00921-6","article-title":"Dezocine promotes T lymphocyte activation and inhibits tumor metastasis after surgery in a mouse model","volume":"38","author":"Song","year":"2020","journal-title":"Invest New Drugs"},{"key":"2025100302441448000_13.5.e011644.7","doi-asserted-by":"crossref","unstructured":"Gupta HV , Tan KS , Fischer GW , et al . Towards a precision approach to anesthetic\/analgesic immunomodulation in cancer. Front Anesthesiol 2024;3. doi:10.3389\/fanes.2024.1464004","DOI":"10.3389\/fanes.2024.1464004"},{"key":"2025100302441448000_13.5.e011644.8","first-page":"467","article-title":"Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors","volume":"32","author":"Kavgaci","year":"2024","journal-title":"Support Care Cancer"},{"key":"2025100302441448000_13.5.e011644.9","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.111611","article-title":"A novel investigation into the negative impact of opioid use on the efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients","volume":"129","author":"Guo","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"2025100302441448000_13.5.e011644.10","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3390\/curroncol31010017","article-title":"Impact of Opioid Use on Duration of Therapy and Overall Survival for Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors","volume":"31","author":"Young","year":"2024","journal-title":"Curr Oncol"},{"key":"2025100302441448000_13.5.e011644.11","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2023.106363","article-title":"The effect of opioids on the efficacy of immunotherapy in recurrent\/metastatic squamous cell carcinoma of the head and neck","volume":"140","author":"Scheff","year":"2023","journal-title":"Oral Oncol"},{"key":"2025100302441448000_13.5.e011644.12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s00432-024-05728-z","article-title":"Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data","volume":"150","author":"Hong","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"2025100302441448000_13.5.e011644.13","doi-asserted-by":"crossref","unstructured":"Scarpa JR , Montagna G , Plitas G , et al . Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer. Front Oncol 2023;13. doi:10.3389\/fonc.2023.1267532","DOI":"10.3389\/fonc.2023.1267532"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-011644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:44:25Z","timestamp":1759484665000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-011644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":13,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,15]]},"published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1136\/jitc-2025-011644"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-011644","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]}}}