Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer
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 modu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1267532/full |
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| author | Joseph R. Scarpa Giacomo Montagna George Plitas Amitabh Gulati Amitabh Gulati Gregory W. Fischer Gregory W. Fischer Joshua S. Mincer Joshua S. Mincer |
| author_facet | Joseph R. Scarpa Giacomo Montagna George Plitas Amitabh Gulati Amitabh Gulati Gregory W. Fischer Gregory W. Fischer Joshua S. Mincer Joshua S. Mincer |
| author_sort | Joseph R. Scarpa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:43:23Z |
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| id | doaj.art-a6bede7dc3a54902a6ef190e48d7c203 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T00:43:23Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a6bede7dc3a54902a6ef190e48d7c2032023-09-15T01:28:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.12675321267532Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancerJoseph R. Scarpa0Giacomo Montagna1George Plitas2Amitabh Gulati3Amitabh Gulati4Gregory W. Fischer5Gregory W. Fischer6Joshua S. Mincer7Joshua S. Mincer8Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United StatesBreast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesBreast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Anesthesiology, Weill Cornell Medicine, New York, NY, United StatesDepartment of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Anesthesiology, Weill Cornell Medicine, New York, NY, United StatesDepartment of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Anesthesiology, Weill Cornell Medicine, New York, NY, United StatesDepartment of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesBackgroundOpioids 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1267532/fullopioidsketamineimmune checkpoint inhibitionanti-PD-L1tumor-infiltrating lymphocytestriple-negative breast cancer |
| spellingShingle | Joseph R. Scarpa Giacomo Montagna George Plitas Amitabh Gulati Amitabh Gulati Gregory W. Fischer Gregory W. Fischer Joshua S. Mincer Joshua S. Mincer Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer Frontiers in Oncology opioids ketamine immune checkpoint inhibition anti-PD-L1 tumor-infiltrating lymphocytes triple-negative breast cancer |
| title | Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer |
| title_full | Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer |
| title_fullStr | Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer |
| title_full_unstemmed | Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer |
| title_short | Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer |
| title_sort | opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple negative breast cancer |
| topic | opioids ketamine immune checkpoint inhibition anti-PD-L1 tumor-infiltrating lymphocytes triple-negative breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1267532/full |
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