Evidence map›Paper›PMID 40664448›Full record

ArticleJournal for immunotherapy of cancer2025

Napsin A-specific T-cell clonotypes are associated with improved clinical outcomes in patients receiving checkpoint immunotherapy for metastatic non-small cell lung cancer.

Natalie J Miller, Christina Baik, Joel W Neal, Fangdi Sun, Rafael Santana-Davila, Sylvia Lee, Keith D Eaton, Renato G Martins, Cristina Rodriguez, Heather Wakelee and 10 more

Abstract read
PubMed Full text at PMC Publisher
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

5 · Who and what money

Authors and funding

20 authors.

Natalie J MillerUniversity of Washington, Seattle, Washington, USA.ORCID http://orcid.org/0000-0002-2467-1349
Christina BaikUniversity of Washington, Seattle, Washington, USA.
Joel W NealDepartment of Medicine, Stanford University, Stanford, California, USA.
Fangdi SunDepartment of Medicine, Stanford University, Stanford, California, USA.
Rafael Santana-DavilaUniversity of Washington, Seattle, Washington, USA.
Sylvia LeeUniversity of Washington, Seattle, Washington, USA.
Keith D EatonUniversity of Washington, Seattle, Washington, USA.
Renato G MartinsVirginia Commonwealth University, Richmond, Virginia, USA.
Cristina RodriguezUniversity of Washington, Seattle, Washington, USA.
Heather WakeleeDepartment of Medicine, Stanford University, Stanford, California, USA.
Sukhmani K PaddaFox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Elena SotilloCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, California, USA.ORCID http://orcid.org/0000-0002-3993-1932
Eric Q KonnickUniversity of Washington, Seattle, Washington, USA.
Alex CamaiFred Hutchinson Cancer Center, Seattle, Washington, USA.
Tatyana PisarenkoFred Hutchinson Cancer Center, Seattle, Washington, USA.
Viswam S NairUniversity of Washington, Seattle, Washington, USA.
Crystal MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, California, USA.
A McGarry HoughtonUniversity of Washington, Seattle, Washington, USA.
Shin-Heng ChiouMedicine, Rutgers Cancer Institute, New Brunswick, New Jersey, USA ditseng@uw.edu shinheng.chiou@rutgers.edu.
Diane TsengUniversity of Washington, Seattle, Washington, USA ditseng@uw.edu shinheng.chiou@rutgers.edu.ORCID http://orcid.org/0000-0002-4420-6399

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI MICHAEL KENNEY · 2007 to 2026
$71.4M
Project 4: Risk stratification for pulmonary nodules detected by CT imaging using plasma and imaging biomarkersP50CA228944 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PHILIP D GREENBERG · 2019 to 2026
$19.6M
NCI NIH HHS P30 CA015704NCI NIH HHS P30 CA124435NCI NIH HHS P50 CA228944
6 · The paper itself

Abstract

backgroundNapsin A is normally expressed in human lung pneumocytes and is a highly expressed cancer antigen in lung adenocarcinoma. We examined whether T cells specific for Napsin A may play a role in immune checkpoint inhibitor (ICI)-mediated responses. We used bulk T-cell receptor (TCR) repertoire data to assess whether the presence of Napsin A-specific clonotypes in the peripheral blood was associated with improved clinical responses to ICI.

methodsPatients with metastatic non-small cell lung cancer (NSCLC) receiving anti-programmed cell death protein 1 (PD-1) and/or programmed death-ligand 1 (PD-L1) were enrolled at Fred Hutchinson Cancer Center and Stanford University Medical Center (n=62; histology of adenocarcinoma n=48, squamous n=9, NSCLC/other n=5). Peripheral blood mononuclear cells were collected for genomic DNA isolation at one pretreatment and one post-treatment time point (range 3 weeks to 3 months). TCRβ was bulk sequenced via the immunoSEQ platform (Adaptive Biotechnologies). Napsin A-specific TCRβ sequences were identified from publicly available data and their frequencies were quantified in each patient sample. We examined whether overall survival (OS) and progression-free survival (PFS) outcomes differed in patients with or without detectable Napsin A-specific TCRs (herein Napsin TCRs). We used Cox proportional hazards regression to assess the association between detectable Napsin TCRs and PFS or OS in univariable and multivariable analyses.

resultsNapsin TCRs were detectable in the blood in a large fraction of our cohort (n=25/62 (40%) pretreatment; n=21/42 (50%) post-treatment). Patients with detectable Napsin TCRs had a significant improvement in OS compared with patients without these TCRs (median OS 45.4 vs 14.8 months, p=0.0043 pretreatment; median OS 55.4 vs 18.9 months, p=0.0066 post-treatment). Among 27

conclusionsNapsin TCRs are frequently detected in patients with NSCLC and are associated with improved OS in patients with NSCLC receiving ICI.

Indexed as

Aspartic Acid EndopeptidasesCarcinoma, Non-Small-Cell LungImmune Checkpoint InhibitorsImmunotherapyLung NeoplasmsT-LymphocytesAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedTreatment OutcomeAspartic Acid EndopeptidasesImmune Checkpoint InhibitorsNAPSA protein, humanBiomarkerImmune Checkpoint InhibitorLung CancerT cellT cell Receptor - TCR

Identifiers

PMID40664448
PMCPMC12265838

What OpenQuestion holds

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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.