Evidence map›Paper›PMID 30081936›Full record

ArticleJournal of translational medicine2018

Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?

Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Massimiliano Salati, Annalinda Pisano, Mazzuca Federica, Maurizio Simmaco, Marianna Nuti, Paolo Marchetti

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 2 pooled it
4.5field-weighted citation impact, top 4% 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

80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.

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  9. Harnessing IDO inhibitors to optimize cancer immunotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
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  11. Mechanisms of primary resistance to immune checkpoint inhibitors in NSCLC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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  12. Article
  13. Archives of medical science : AMS · 2025
    Article
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Andrea BotticelliDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1037, 00189, Rome, Italy. andreabotticelli@hotmail.it.
Bruna CerbelliDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
Luana LionettoExperimental Immunology Laboratory, Biochemistry Laboratory, IDI-IRCCS FLMM, Rome, Italy.
Ilaria ZizzariDepartment of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
Massimiliano SalatiDepartment of Oncology, Università di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy.
Annalinda PisanoDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
Mazzuca FedericaDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1037, 00189, Rome, Italy.
Maurizio SimmacoAdvanced Molecular Diagnostics Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
Marianna NutiDepartment of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
Paolo MarchettiDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1037, 00189, Rome, Italy.
Sapienza University of Rome · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITPoliclinico di Modena · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25-30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment.

methodsPre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann-Whitney test.

resultsTwenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (< 3 months) to nivolumab treatment. The median value of kyn/trp ratio was 0.06 µg/ml and the median value of quinolinic acid was 68.45 ng/ml. A significant correlation between early progression and higher kyn/trp ratio and quinolinic acid concentration was observed (p = 0.017 and p = 0.005, respectively). Patients presenting lower values of kyn/trp ratio and quinolinic acid levels showed longer PFS (median PFS not reached versus 3 months; HR: 0.3; p = 0.018) and OS (median OS not reached vs 3 months; HR: 0.18; p = 0.0005).

conclusionIDO activity, expressed as kyn/trp ratio, is associated with response to immunotherapy; in particular, higher kyn/trp ratio could predict resistance to anti-PD-1 treatment. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in those patients with high level of kyn/trp ratio.

Indexed as

Drug Resistance, NeoplasmAgedCarcinoma, Non-Small-Cell LungDisease ProgressionFemaleHumansImmunotherapyIndoleamine-Pyrrole 2,3,-DioxygenaseKaplan-Meier EstimateKynurenineLung NeoplasmsMaleMultivariate AnalysisProgrammed Cell Death 1 ReceptorQuinolinic AcidTryptophanIndoleamine-Pyrrole 2,3,-DioxygenaseKynureninePDCD1 protein, humanProgrammed Cell Death 1 ReceptorQuinolinic AcidTryptophanAnti-PD-1IDOImmunotherapyKynurenineNivolumab

Identifiers

PMID30081936
PMCPMC6080500
OpenAlexW2887169335

What OpenQuestion holds

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LicenceCC BY
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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.