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

Frontiers in Oncology

Oncology

Giacomo Montagna¹  George Plitas¹  Joseph R. Scarpa²  Amitabh Gulati³  Joshua S. Mincer³  Gregory W. Fischer³ 

[1] Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States;Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States;Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States;Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States;

关键词: opioids;    ketamine;    immune checkpoint inhibition;    anti-PD-L1;    tumor-infiltrating lymphocytes;    triple-negative breast cancer;   

DOI  :  10.3389/fonc.2023.1267532

 received in 2023-07-26, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundOpioids 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.MethodsTumor 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.ResultsWe 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.ConclusionsOpioids 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.

【 授权许可】

Unknown   
Copyright © 2023 Scarpa, Montagna, Plitas, Gulati, Fischer and Mincer