Evidence map›Paper›PMID 33757546›Full record

ArticleJournal of translational medicine2021

The role of opioids in cancer response to immunotherapy.

Andrea Botticelli, Alessio Cirillo, Giulia Pomati, Bruna Cerbelli, Simone Scagnoli, Michela Roberto, Alain Gelibter, Giulia Mammone, Maria Letizia Calandrella, Edoardo Cerbelli and 6 more

Open access · goldAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 3 pooled it
5.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. The impact of cannabis on immune checkpoint inhibitor therapy: a systematic review of immunomodulatory effects of cannabis in patients with and without cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
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  5. Opioids and immunosuppression in patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
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  10. Cancer and neurotransmitter receptors.Chinese medical journal · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Andrea Botticelli *Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185, Rome, Italy.
Alessio Cirillo *Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Giulia PomatiDepartment of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161, Rome, Italy. giulia.pomati@uniroma1.it.ORCID http://orcid.org/0000-0001-6715-5443
Bruna CerbelliDepartment of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Simone ScagnoliDepartment of Medical and Surgical Sciences and Translational Medicine, University of Rome Sapienza, 00185, Rome, Italy.
Michela RobertoDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, 00185, Rome, Italy.
Alain GelibterDepartment of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Giulia MammoneDepartment of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Maria Letizia CalandrellaDepartment of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Edoardo CerbelliDepartment of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Francesca Romana Di PietroIstituto Dermopatico Dell'Immacolata, IDI-IRCCS, 00167, Rome, Italy.
Federica De GalitiisIstituto Dermopatico Dell'Immacolata, IDI-IRCCS, 00167, Rome, Italy.
Gaetano LanzettaMedical Oncology Unit, Italian Neuro-Traumatology Institute, 00046, Grottaferrata, Italy.
Enrico CortesiDepartment of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Silvia Mezi *Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185, Rome, Italy.
Paolo Marchetti *Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185, Rome, Italy.
Sapienza University of Rome · ITIstituto Dermopatico dell'Immacolata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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. 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.

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.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAnalgesics, OpioidHumansImmunotherapyRetrospective StudiesAnalgesics, OpioidEarly progressionImmunotherapyOpioid receptorsOpioidsPredictive factorPrognostic factor

Identifiers

PMID33757546
PMCPMC7988927
OpenAlexW3127054550

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.