The role of opioids in cancer response to immunotherapy

Journal of Translational Medicine

Paolo Marchetti¹  Andrea Botticelli¹  Michela Roberto¹  Simone Scagnoli²  Giulia Pomati³  Silvia Mezi⁴  Alain Gelibter⁴  Bruna Cerbelli⁴  Giulia Mammone⁴  Enrico Cortesi⁴  Edoardo Cerbelli⁴  Maria Letizia Calandrella⁴  Alessio Cirillo⁴  Francesca Romana Di Pietro⁵  Federica De Galitiis⁵  Gaetano Lanzetta⁶ 

[1] Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185, Rome, Italy;Department of Medical and Surgical Sciences and Translational Medicine, University of Rome Sapienza, 00185, Rome, Italy;Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161, Rome, Italy;Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy;Istituto Dermopatico Dell’Immacolata, IDI-IRCCS, 00167, Rome, Italy;Medical Oncology Unit, Italian Neuro-Traumatology Institute, 00046, Grottaferrata, Italy;

关键词: Immunotherapy;    Opioids;    Opioid receptors;    Prognostic factor;    Predictive factor;    Early progression;   

DOI  :  10.1186/s12967-021-02784-8

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsThis 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.ResultsOne 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.DiscussionOur 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.ConclusionsA 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.

【 授权许可】

CC BY