ArticleJournal for immunotherapy of cancer2024
Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- The effect of the Emotional Freedom Technique (EFT) on pain and depression in cancer patients: a randomized controlled trial.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Trial
- Intraoperative esketamine for postoperative analgesia and depression in pancreatic cancer surgery: protocol for a multicenter randomized controlled trial.Annals of medicine · 2026Article
- Cancer-related pain: A bidirectional modulator of cancer progression.Clinical and translational medicine · 2026Review
- When immunotherapy hurts: neoadjuvant PD-1 inhibitors increase opioid use after mastectomy with reconstruction.Breast cancer research and treatment · 2026Article
- Crosstalk Between Opioids and the Anti-Tumour Immune Checkpoint Axis.Current oncology (Toronto, Ont.) · 2026Review
- Radiotherapy-Associated Pain in Head and Neck Cancer: From Clinical Burden to Neuroimmune Modulator.Journal of clinical medicine · 2026Review
- Impact of baseline medications on real-world overall survival in immune checkpoint inhibitor-treated patients with cancer in the RADIOHEAD cohort.Med (New York, N.Y.) · 2026Article
- A targetable opioid/cancer associated fibroblast axis drives extracellular matrix remodeling and tumor aggressiveness in pancreatic cancer.bioRxiv : the preprint server for biology · 2026Article
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Circadian Rhythm Genes-based Prognostic Signature for Bladder Cancer: Association of EZH2 Expression with Anesthetic-related Changes in Circulating Tumor Cells.Current medicinal chemistry · 2026Article
- Enteric neuro-immune-tumor ecosystem in pancreatic, colorectal, and gastric malignancies: context dependence and translational priorities.Frontiers in immunology · 2026Review
- Sestrin2 Knockdown Impairs Proliferation, Migration, Invasion, and Apoptosis in OSCC Cells via PI3K/AKT/mTOR and MAPK Pathways.Current issues in molecular biology · 2025Article
- OPIOID-EXPRESSING B CELLS SILENCE TUMOR-INFILTRATING NOCICEPTOR NEURONS.Research square · 2025Article
- Mending the divide: integrating opioid analgesia and immunotherapy for optimal cancer care.Journal for immunotherapy of cancer · 2025Article
- Review
- Exploring the possible mechanism of low-dose naloxone exposure improving the immune microenvironment of gastric cancer tumors.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundImmune checkpoint inhibitors (ICIs) are becoming the standard of care for recurrent and metastatic cancer. Opioids, the primary treatment for cancer-related pain, are immunosuppressive raising concerns about their potential to interfere with the efficacy of ICIs. We hypothesize that exogenous opioids given for analgesia suppress antitumor immunity via T cell-mediated mu opioid receptor 1 (OPRM1) signaling.
methodsIn silico bioinformatics were used to assess OPRM1 receptor expression on tumor-infiltrating immune cells in patients with head and neck squamous cell carcinoma (HNSCC) and across different cancer types. A syngeneic orthotopic mouse model of oral squamous cell carcinoma was used to study the impact of morphine and OPRM1 antagonism on tumor-infiltrating immune cells, tumor growth and antitumor efficacy of anti-Programmed cell death protein 1 (PD-1) monoclonal antibody treatment.
resultsIn patients with HNSCC, OPRM1 expression was most abundant in CD8+ T cells, particularly in patients who had not been prescribed opioids prior to resection and exhibited increased expression of exhaustion markers. Exogenous morphine treatment in tumor-bearing mice reduced CD4+ and CD8+ T-cell infiltration and subsequently anti-PD1 ICI efficacy. Peripherally acting mu opioid receptor antagonism, when administered in the adjunctive setting, was able to block morphine-induced immunosuppression and recover the antitumor efficacy of anti-PD1.
conclusionsThese findings suggest that morphine acts via a peripheral OPRM1-mediated mechanism to suppress CD8+ T cells, thereby fostering a pro-tumor-impaired immune response. Importantly, peripherally-restricted OPRM1 antagonism can effectively block this morphine-induced immunosuppression while still allowing for centrally-mediated analgesia, indicating a potential therapeutic strategy for mitigating the adverse effects of opioid pain relief in cancer treatment.
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