Evidence map›Paper›PMID 41691240›Full record

ArticleJournal of translational medicine2026

The immunological fitness of NSCLC patients drives the response to anti-PD1-based immunotherapy regardless of age.

Lucrezia Tuosto, Alain Gelibter, Lidia Strigari, Angela Asquino, Marco Siringo, Angelica Pace, Flavio Valentino, Davide Capozzi, Serena Bianchini, Filippo Bellati and 5 more

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Lucrezia TuostoLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Alain GelibterDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. alain.gelibter@uniroma1.it.
Lidia StrigariDepartment of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, 40138, Bologna, Italy.
Angela AsquinoLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Marco SiringoDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
Angelica PaceLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Flavio ValentinoLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Davide CapozziLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Serena BianchiniLaboratory of Seminology-Sperm Bank "Loredana Gandini", Department of Experimental Medicine, "Sapienza" University of Rome, 00161, Rome, Italy.
Filippo BellatiDepartment of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189, Rome, Italy.
Daniele SantiniDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
Marianna NutiLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Ilaria Grazia ZizzariLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Aurelia RughettiLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. aurelia.rughetti@uniroma1.it.
Chiara NapoletanoLaboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. chiara.napoletano@uniroma1.it.ORCID 0000-0001-5449-5430

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOver the past decade, the number of elderly cancer patients has increased, including those with NSCLCs, most of whom are over 60 years old. NSCLC patients receive anti-PD1-based therapies. These therapies directly target the immune system by activating T cells. However, older patients exhibit several baseline immune system changes compared to their younger counterparts, which could affect treatment effectiveness. This study aims to assess the immune systems of younger (<65) and older (≥65) NSCLC patients at baseline to determine whether immune aging may alter the efficacy of immune treatments.

methodsSeventy-eight NSCLC patients were enrolled in this study and divided into two groups on an age basis: younger (26 pts, < 65 years; young-pts) and older (52 pts, ≥65 years; old-pts). The patient’s immune profile was assessed before therapy by evaluating circulating immune cell subsets and soluble immune mediators using flow cytometry and a Luminex assay, respectively. Immune populations and soluble factors were correlated with treatment response and survival outcomes. A cohort of 27 healthy donors (HDs) served as the control group.

resultsCancer patients (CPs) exhibited higher levels of CD8 (p < 0.001), Ki67 (p < 0.001), effector (p < 0.0075), and regulatory T cells (p < 0.001) than HDs. These differences remained consistent across age groups, except for effector cells, which showed a slight increase (p = 0.0932) in young-CPs compared with young-HDs. Moreover, CD3 (p < 0.001), CD4 (p < 0.001), PD1 (p < 0.001), and naïve T cells (p = 0.0144) were significantly lower in CPs than in HDs, with a similar trend across age groups, except for naïve T cells (p = 0.0748). The OS data showed no differences between the young and old groups when analyzing the entire population and the responder patients (Rs). However, young non-responders (NRs) experienced longer survival than older NRs. Multivariate analysis identified PMN (Lox1+)-MDSCs, Ki67, and response to therapy as independent predictors in NRs. The ROC curve established the cut-off for distinguishing the high-risk group, characterized by worse outcomes with elevated levels of PMN (Lox1+)-MDSCs and Ki67+ T cells, from the low-risk group (log-rank p = 0.0093). Moreover, old-NRs showed significantly higher levels of PMN (Lox1+)-MDSCs than old-Rs, and a higher percentage of CD137+PD1+ (p = 0.05) and central memory T cells (p = 0.09).

conclusionThe combined index of PMN(Lox1+)-MDSCs and Ki67+ T cells offers a practical tool for assessing immunological fitness in the NR setting, thereby enhancing patient stratification.

Indexed as

Carcinoma, Non-Small-Cell LungImmune Checkpoint InhibitorsLung NeoplasmsProgrammed Cell Death 1 ReceptorAgedAged, 80 and overAge FactorsAgingCase-Control StudiesCD8-Positive T-LymphocytesCell SeparationDrug Resistance, NeoplasmFemaleFlow CytometryHumansMaleImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptoranti-PD1 treatmentElderly patientsImmunotherapyNon-small cell lung cancer

Identifiers

PMID41691240
PMCPMC13011409

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