Concomitant use of analgesics and immune checkpoint inhibitors in non-small cell lung cancer: A pharmacodynamics perspective

Eur J Pharmacol. 2021 Sep 5:906:174284. doi: 10.1016/j.ejphar.2021.174284. Epub 2021 Jun 24.

Abstract

The invention of immunotherapy, such as immune checkpoint inhibitors (ICIs) for advanced-stage non-small cell lung cancer (NSCLC), has become a new standard of care for a defined group of NSCLC patients. However, the possible impacts of ICI interactions with analgesics for alleviating cancer-related pain are unclear and lack clinical evidence. Many studies have indicated that opioids detrimentally affect the immune system, possibly harming patients of ongoing immunotherapy. Opioids may repress the immune system in various ways, including impairing T cell function, upregulating immunosuppressor Treg cells, and interrupting intestinal microflora composition that disrupts the entire immune system. Furthermore, opioids can influence tumor progression and metastasis directly as opioid receptors are overexpressed in several types of NSCLC. In contrast, another analgesic acting on cyclooxygenase (COX) inhibition (i.e., NSAIDs) may be a candidate for adjuvant therapy since COX-2 is also expressed in the tumor cells of NSCLC patients. In addition, COX-2 is associated with tumor proliferation and metastasis. Therefore, both prospective and retrospective studies should confirm the advantages and disadvantages of the concurrent use of analgesics and ICIs in a clinical setting.

Keywords: Gut microbiota; Immune checkpoint blockers; NSAIDs; Opioids; T-lymphocyte.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Analgesics, Opioid / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Interactions
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immune Checkpoint Inhibitors / immunology
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lung Neoplasms / drug therapy*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Analgesics, Opioid
  • Cyclooxygenase 2 Inhibitors
  • Immune Checkpoint Inhibitors