Evidence map›Paper›PMID 31402427›Full record

ArticleInvestigational new drugs2020

Germinal Immunogenetics predict treatment outcome for PD-1/PD-L1 checkpoint inhibitors.

Sadal Refae, Jocelyn Gal, Nathalie Ebran, Josiane Otto, Delphine Borchiellini, Frederic Peyrade, Emmanuel Chamorey, Patrick Brest, Gérard Milano, Esma Saada-Bouzid

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Investigational new drugs, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 11% 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.

  1. Pooled it
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  14. The Current and Future of Biomarkers of Immune Related Adverse Events.Rheumatic diseases clinics of North America · 2024
    Review
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  18. [Advances in Predictive Research of Immune Checkpoint Inhibitors-related 
Adverse Events].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Sadal RefaeCentre Antoine Lacassagne, University Côte d'Azur, Oncopharmacology Unit, F-06189, Nice, France.
Jocelyn GalCentre Antoine Lacassagne, Epidemiology and Biostatistics Department, University Côte d'Azur, F-06189, Nice, France.
Nathalie EbranCentre Antoine Lacassagne, University Côte d'Azur, Oncopharmacology Unit, F-06189, Nice, France.
Josiane OttoCentre Antoine Lacassagne, Medical Oncology Department, University Côte d'Azur, F-06189, Nice, France.
Delphine BorchielliniCentre Antoine Lacassagne, Medical Oncology Department, University Côte d'Azur, F-06189, Nice, France.
Frederic PeyradeCentre Antoine Lacassagne, Medical Oncology Department, University Côte d'Azur, F-06189, Nice, France.
Emmanuel ChamoreyCentre Antoine Lacassagne, Epidemiology and Biostatistics Department, University Côte d'Azur, F-06189, Nice, France.
Patrick BrestCentre Antoine Lacassagne, CNRS, Inserm, Ircan, FHU-Oncoage, University Côte d'Azur, F-06189, Nice, France.
Gérard MilanoCentre Antoine Lacassagne, University Côte d'Azur, Oncopharmacology Unit, F-06189, Nice, France. gerard.milano@nice.unicancer.fr.
Esma Saada-BouzidCentre Antoine Lacassagne, Medical Oncology Department, University Côte d'Azur, F-06189, Nice, France. esma.saada-bouzid@nice.unicancer.fr.
Centre Antoine Lacassagne · FRInstitut National de Recherche en Santé Publique · ML

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Checkpoint inhibitors bring marked benefits but only in a minority of patients and may also be associated with severe adverse events. Treatment outcome still cannot be faithfully predicted. The following study hypothesized that host genetics could be applied as predictive biomarkers for checkpoint inhibitor response and immune-related adverse events. We conducted a study based on germinal polymorphisms from genes coding for proteins involved in immune regulation. Methods Germinal DNA was obtained from advanced cancer patients treated with anti-PD-1/PD-L1 checkpoint inhibitors. DNA was genotyped using a custom panel of 166 single nucleotide polymorphisms covering 86 preselected immunogenetic-related genes. Computational analysis using a GTEX portal was made to determine potential expression Quantitative Trait Loci in tissues. Results Ninety-four consecutive patients were included. Objective response rate (complete or partial response) was significantly correlated to tumor microenvironment-related SNPs concerning CCL2, NOS3, IL1RN, IL12B, CXCR3 and IL6R genes. Toxicity were linked to target-related gene SNPs including UNG, IFNW1, CTLA4, PD-L1 and IFNL4 genes. The Area Under the ROC curve (AUC) was 0.81 (95% CI: 0.72-0.9) for response and 0.89 (95% CI: 0.76-1.00) for toxicity. In silico functionality exploring pointed rs4845618 (IL6R), rs10964859 (IFNW1) and rs3087243 (CTLA4) as potentially impacting gene expression. Conclusion These results strongly support a role for distinct immunogenetic-related gene SNPs able to predict efficacy and safety of anti-PD1/PD-L1 therapies. The results highlight the existence of patient-specific, germinal biomarkers able predict response to checkpoint inhibitor efficacy and, possibly, to predict treatment-related adverse events.

Indexed as

Germ-Line MutationImmunogeneticsAdultAgedAged, 80 and overAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorFemaleFollow-Up StudiesHumansImmunotherapyMaleMiddle AgedNeoplasmsPharmacogenomic TestingAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD274 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorGerminal polymorphismsImmunotherapyPrecision medicinePredictive test

Identifiers

PMID31402427
OpenAlexW2967332802

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.