Evidence map›Paper›PMID 40889797›Full record

ArticleJournal for immunotherapy of cancer2025

Regulatory polymorphisms of

Martina Esposito, Sara Noci, Francesca Minnai, Tania Camboni, Eleonora Mangano, Manuela Gariboldi, Elisa Frullanti, Claudia Bareggi, Elena Collovà, Serena Girelli and 7 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

17 authors.

Martina EspositoInstitute for Biomedical Technologies, National Research Council, Segrate, MI, Italy.
Sara NociDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Francesca MinnaiInstitute for Biomedical Technologies, National Research Council, Segrate, MI, Italy.
Tania CamboniInstitute for Biomedical Technologies, National Research Council, Segrate, MI, Italy.
Eleonora ManganoInstitute for Biomedical Technologies, National Research Council, Segrate, MI, Italy.
Manuela GariboldiDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Elisa FrullantiMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Claudia BareggiSC Medical Oncology, Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milano, Lombardia, Italy.
Elena CollovàMedical Oncology Unit, ASST Ovest Milanese, Legnano, Lombardy, Italy.
Serena GirelliMedical Oncology Unit, Fatebenefratelli Hospital, ASST Fatebenefratelli Sacco, Milan, Italy.
Sheila PivaMedical Oncology Unit, Fatebenefratelli Hospital, ASST Fatebenefratelli Sacco, Milan, Italy.
Gabriella FarinaMedical Oncology Unit, Fatebenefratelli Hospital, ASST Fatebenefratelli Sacco, Milan, Italy.
Arianna PagliaroMedical Oncology & Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy.
Luca ToschiMedical Oncology & Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy.
Luca SalaSC Medical Oncology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Diego Luigi CortinovisSC Medical Oncology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.ORCID http://orcid.org/0000-0001-7611-7369
Francesca ColomboInstitute for Biomedical Technologies, National Research Council, Segrate, MI, Italy francesca.colombo@cnr.it.ORCID http://orcid.org/0000-0003-2015-4317

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors (ICI) improved survival of patients with non-small cell lung cancer (NSCLC), yet many patients do not respond to treatment. The identification of markers for ICI response remains an unmet clinical need. This study hypothesizes that host genetics influences the response to ICI, contributing to the variability in efficacy among individuals.

methodsWe conducted a genome-wide association study (GWAS) in patients with NSCLC on ICI monotherapy with nivolumab, pembrolizumab, or atezolizumab, to identify germline variants associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) at 24 months after the start of ICI therapy. Genomic DNA was genotyped using Axiom Precision Medicine Research Arrays. Raw data were processed with Axiom Analysis Suite, and quality checked with PLINK software. Imputation to the whole genome was done on the Michigan Imputation Server. Association analyses were performed for ORR (logistic regression with PLINK2 software) and survival (Cox proportional hazards model, with GenAbel package in R environment), with appropriate covariates. Variants were annotated for functional significance using SNPnexus and FUMA. Post-GWAS analyses, including colocalization, were performed to explore the function of the identified variants. Their possible role as expression quantitative trait loci was investigated in different databases (GTEx, eQTLGen, TCGA).

resultsNo genome-wide significant associations were found for ORR or PFS, while a locus on chromosome 2 (lead variant: rs111648355) showed near genome-wide significance (p value=6.3×10⁻⁸) for OS. Patients with minor alleles of these variants exhibited significantly worse OS (HR=5.1, 95% CI: 2.9 to 9.2). Functional annotation linked these variants to regulatory effects on genes including

conclusionsThis study identifies an association between a genomic locus on chromosome 2 and OS in patients with NSCLC treated with ICI. Although these results need validation in larger cohorts and functional studies to elucidate the underlying mechanisms, they highlight the potential of germline variants as predictive biomarkers of response to ICI.

Indexed as

Carcinoma, Non-Small-Cell LungDNA-Binding ProteinsImmune Checkpoint InhibitorsImmunotherapyLung NeoplasmsMutS Homolog 2 ProteinAgedFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideDNA-Binding ProteinsG-T mismatch-binding proteinImmune Checkpoint InhibitorsMSH2 protein, humanMutS Homolog 2 ProteinGeneticGenomeImmune Checkpoint InhibitorsNon-Small Cell Lung Cancer

Identifiers

PMID40889797
PMCPMC12406856

What OpenQuestion holds

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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.