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The role of opioids in cancer response to immunotherapy

BACKGROUND: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activi...

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Autores principales: Botticelli, Andrea, Cirillo, Alessio, Pomati, Giulia, Cerbelli, Bruna, Scagnoli, Simone, Roberto, Michela, Gelibter, Alain, Mammone, Giulia, Calandrella, Maria Letizia, Cerbelli, Edoardo, Di Pietro, Francesca Romana, De Galitiis, Federica, Lanzetta, Gaetano, Cortesi, Enrico, Mezi, Silvia, Marchetti, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988927/
https://www.ncbi.nlm.nih.gov/pubmed/33757546
http://dx.doi.org/10.1186/s12967-021-02784-8
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author Botticelli, Andrea
Cirillo, Alessio
Pomati, Giulia
Cerbelli, Bruna
Scagnoli, Simone
Roberto, Michela
Gelibter, Alain
Mammone, Giulia
Calandrella, Maria Letizia
Cerbelli, Edoardo
Di Pietro, Francesca Romana
De Galitiis, Federica
Lanzetta, Gaetano
Cortesi, Enrico
Mezi, Silvia
Marchetti, Paolo
author_facet Botticelli, Andrea
Cirillo, Alessio
Pomati, Giulia
Cerbelli, Bruna
Scagnoli, Simone
Roberto, Michela
Gelibter, Alain
Mammone, Giulia
Calandrella, Maria Letizia
Cerbelli, Edoardo
Di Pietro, Francesca Romana
De Galitiis, Federica
Lanzetta, Gaetano
Cortesi, Enrico
Mezi, Silvia
Marchetti, Paolo
author_sort Botticelli, Andrea
collection PubMed
description BACKGROUND: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities. METHODS: This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival. RESULTS: One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37–2.09, p < 0.0001; median OS, 4 months vs. 35 months, HR 1.60, 95% CI 1.26–2.02, p < 0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥ 1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden. DISCUSSION: Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well. CONCLUSIONS: A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.
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spelling pubmed-79889272021-03-25 The role of opioids in cancer response to immunotherapy Botticelli, Andrea Cirillo, Alessio Pomati, Giulia Cerbelli, Bruna Scagnoli, Simone Roberto, Michela Gelibter, Alain Mammone, Giulia Calandrella, Maria Letizia Cerbelli, Edoardo Di Pietro, Francesca Romana De Galitiis, Federica Lanzetta, Gaetano Cortesi, Enrico Mezi, Silvia Marchetti, Paolo J Transl Med Research BACKGROUND: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities. METHODS: This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival. RESULTS: One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37–2.09, p < 0.0001; median OS, 4 months vs. 35 months, HR 1.60, 95% CI 1.26–2.02, p < 0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥ 1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden. DISCUSSION: Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well. CONCLUSIONS: A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes. BioMed Central 2021-03-23 /pmc/articles/PMC7988927/ /pubmed/33757546 http://dx.doi.org/10.1186/s12967-021-02784-8 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Botticelli, Andrea
Cirillo, Alessio
Pomati, Giulia
Cerbelli, Bruna
Scagnoli, Simone
Roberto, Michela
Gelibter, Alain
Mammone, Giulia
Calandrella, Maria Letizia
Cerbelli, Edoardo
Di Pietro, Francesca Romana
De Galitiis, Federica
Lanzetta, Gaetano
Cortesi, Enrico
Mezi, Silvia
Marchetti, Paolo
The role of opioids in cancer response to immunotherapy
title The role of opioids in cancer response to immunotherapy
title_full The role of opioids in cancer response to immunotherapy
title_fullStr The role of opioids in cancer response to immunotherapy
title_full_unstemmed The role of opioids in cancer response to immunotherapy
title_short The role of opioids in cancer response to immunotherapy
title_sort role of opioids in cancer response to immunotherapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988927/
https://www.ncbi.nlm.nih.gov/pubmed/33757546
http://dx.doi.org/10.1186/s12967-021-02784-8
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