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Research progress on the impact of opioids on the tumor immune microenvironment (Review)

  • Authors:
    • Yuancheng Zhou
    • Wenyu Li
    • Yuanji Chen
    • Xudong Hu
    • Chuanwang Miao
  • View Affiliations / Copyright

    Affiliations: Department of Preventive Medicine, (Institute of Radiation Medicine), Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 251016, P.R. China, The Second School of Clinical Medicine of Binzhou Medical University, Anesthesiology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 53
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    Published online on: April 15, 2025
       https://doi.org/10.3892/mco.2025.2848
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Abstract

Opioids have been extensively used in cancer pain management because they can significantly improve the quality of life of patients with advanced cancer. However, recent evidence suggests that opioids can also modulate the tumor immune microenvironment by interacting with opioid receptors on immune cells, potentially regulating tumor progression and efficacy of cancer treatments. Notably, morphine can exhibit a dose‑dependent effect on tumor immunity in pancreatic cancer and renal cell models, with lower doses potentially promoting tumor migration and invasion of pancreatic cancer cells, whereas higher doses shows the effect of inhibiting migration and invasion through distinct molecular pathways. The present review therefore comprehensively explored the mechanisms by which opioids can regulate the tumor immune microenvironment, focusing on their effects on immune cells, oxidative stress and angiogenesis. It also examined the interactions between opioids and other analgesics, along with their potential impact on immune modulation. All relevant articles and materials were retrieved from PubMed using the key words ‘opioids’, ‘immune system’, ‘T cells’, ‘monocytes’, ’macrophages’, ‘lymphocytes’, ‘natural killer cell’, ‘immunotherapy’, ‘immune cell function’ and ‘dose dependent effect’. The immunosuppressive effects of opioids, particularly through the µ‑opioid receptor, can suppress the activity of natural killer cells, impair antigen presentation and promote the function of regulatory T cells (Tregs). These effects may contribute to tumor progression and metastasis. The severity of these immunosuppressive effects appears to be dose‑dependent and can vary among different tumor types. There is evidence to suggest that tumors with higher immune responsiveness will experience more pronounced suppression, including the reduction of tumor angiogenesis, resulting in a decrease in tumor volume and decrease in tumor metastases. Furthermore, the combination of opioids with other analgesics, such as non‑steroidal anti‑inflammatory drugs, has the potential to exacerbate immunosuppression, which can in turn increase the risk of infections. Therefore, although opioids are essential for pain management in patients with cancer, their potential to modulate the immune microenvironment and promote tumor progression requires careful consideration. Clinicians should evaluate the advantages and disadvantages of opioids, especially regarding emerging immunotherapies, to minimize their potential negative effects on the outcomes of cancer treatments. Future studies are recommended to prioritize the development of strategies that optimize pain management whilst preserving immune function, such as receptor‑specific opioid formulations or adjunctive therapies targeting immunosuppressive pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou Y, Li W, Chen Y, Hu X and Miao C: Research progress on the impact of opioids on the tumor immune microenvironment (Review). Mol Clin Oncol 22: 53, 2025.
APA
Zhou, Y., Li, W., Chen, Y., Hu, X., & Miao, C. (2025). Research progress on the impact of opioids on the tumor immune microenvironment (Review). Molecular and Clinical Oncology, 22, 53. https://doi.org/10.3892/mco.2025.2848
MLA
Zhou, Y., Li, W., Chen, Y., Hu, X., Miao, C."Research progress on the impact of opioids on the tumor immune microenvironment (Review)". Molecular and Clinical Oncology 22.6 (2025): 53.
Chicago
Zhou, Y., Li, W., Chen, Y., Hu, X., Miao, C."Research progress on the impact of opioids on the tumor immune microenvironment (Review)". Molecular and Clinical Oncology 22, no. 6 (2025): 53. https://doi.org/10.3892/mco.2025.2848
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Y, Li W, Chen Y, Hu X and Miao C: Research progress on the impact of opioids on the tumor immune microenvironment (Review). Mol Clin Oncol 22: 53, 2025.
APA
Zhou, Y., Li, W., Chen, Y., Hu, X., & Miao, C. (2025). Research progress on the impact of opioids on the tumor immune microenvironment (Review). Molecular and Clinical Oncology, 22, 53. https://doi.org/10.3892/mco.2025.2848
MLA
Zhou, Y., Li, W., Chen, Y., Hu, X., Miao, C."Research progress on the impact of opioids on the tumor immune microenvironment (Review)". Molecular and Clinical Oncology 22.6 (2025): 53.
Chicago
Zhou, Y., Li, W., Chen, Y., Hu, X., Miao, C."Research progress on the impact of opioids on the tumor immune microenvironment (Review)". Molecular and Clinical Oncology 22, no. 6 (2025): 53. https://doi.org/10.3892/mco.2025.2848
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