Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer.

TitleOpioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer.
Publication TypeJournal Article
Year of Publication2023
AuthorsScarpa JR, Montagna G, Plitas G, Gulati A, Fischer GW, Mincer JS
JournalFront Oncol
Volume13
Pagination1267532
Date Published2023
ISSN2234-943X
Abstract

BACKGROUND: Opioids are the primary analgesics for cancer pain. Recent clinical evidence suggests opioids may counteract the effect of immune checkpoint inhibition (ICI) immunotherapy, but the mechanism for this interaction is unknown. The following experiments study how opioids and immunotherapy modulate a common RNA expression pathway in triple negative breast cancer (TNBC), a cancer subtype in which immunotherapy is increasingly used. This study identifies a mechanism by which opioids may decrease ICI efficacy, and compares ketamine, a non-opioid analgesic with emerging use in cancer pain, for potential ICI interaction.

METHODS: Tumor RNA expression and clinicopathologic data from a large cohort with TNBC (N=286) was used to identify RNA expression signatures of disease. Various drug-induced RNA expression profiles were extracted from multimodal RNA expression datasets and analyzed to estimate the RNA expression effects of ICI, opioids, and ketamine on TNBC.

RESULTS: We identified a RNA expression network in CD8+ T-cells that was relevant to TNBC pathogenesis and prognosis. Both opioids and anti-PD-L1 ICI regulated RNA expression in this network, suggesting a nexus for opioid-ICI interaction. Morphine and anti-PD-L1 therapy regulated RNA expression in opposing directions. By contrast, there was little overlap between the effect of ketamine and anti-PD-L1 therapy on RNA expression.

CONCLUSIONS: Opioids and ICI may target a common immune network in TNBC and regulate gene expression in opposing fashion. No available evidence supports a similar interaction between ketamine and ICI.

DOI10.3389/fonc.2023.1267532
Alternate JournalFront Oncol
PubMed ID37781176
PubMed Central IDPMC10539607
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States