Evidence map›Paper›PMID 41634004›Full record

ArticleNature communications2026

Metabolic characterization of tumor-immune interactions by multiplexed immunofluorescence reveals spatial mechanisms of immunotherapy response in non-small cell lung carcinoma (NSCLC).

James Monkman, Aaron Kilgallon, Clara Lawler, Rafael Tubelleza, Thazin Nwe Aung, Jonathan H Warrell, Ioannis Vathiotis, Ioannis P Trontzas, Niki Gavrielatou, Nay Nwe Nyein Chan and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

16 authors.

James MonkmanFrazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.ORCID http://orcid.org/0000-0002-7219-8402
Aaron KilgallonFrazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.ORCID http://orcid.org/0000-0003-1450-0009
Clara LawlerFrazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.ORCID http://orcid.org/0000-0001-7208-9225
Rafael TubellezaFrazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Thazin Nwe AungDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4150-0426
Jonathan H WarrellDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-1323-4602
Ioannis VathiotisDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-1772-5986
Ioannis P TrontzasDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Niki GavrielatouDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-1380-6831
Nay Nwe Nyein ChanDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0009-0006-1633-6125
Rotem CzertokNucleai, Tel-Aviv, Israel.
Shai BooksteinNucleai, Tel-Aviv, Israel.ORCID http://orcid.org/0009-0002-5132-4024
Ken O'ByrnePrincess Alexandra Hospital, Woolloongabba, QLD, Australia.
Ettai MarkovitsNucleai, Tel-Aviv, Israel.
David L RimmDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5820-4397
Arutha KulasingheFrazer Institute, The University of Queensland, Woolloongabba, QLD, Australia. Arutha.kulasinghe@uq.edu.au.ORCID http://orcid.org/0000-0003-3224-7350

Funding

PA Research Foundation (Princess Alexandra Research Foundation) AK
6 · The paper itself

Abstract

Immune checkpoint inhibitors (ICI) have improved clinical outcomes for some patients with advanced NSCLC, however a substantial proportion of patients remain treatment resistant. Here we analyze the NSCLC tumor microenvironment (TME) using multiplexed immunofluorescence (mIF) of biopsies taken from patients prior to ICI treatment. We apply a deep-learning model to classify the cellular phenotypes and probe functional and metabolic states of both tumor and immune cells, aiming to reveal predictive features of response to ICI. Tissue neighborhoods are generated to allow geometric profiling of spatial densities and interactions at a range of scales. Multivariate modelling of ICI response yields a model that predicts progression-free survival (PFS) over 24 months (AUC = 0.8). The selected features in the model imply a role for cell-cell proximities within discrete metabolic contexts. These tissue insights may supplement our understanding of the current paradigms around classical immunology in the NSCLC TME and its influence on immunotherapy outcomes.

Indexed as

Carcinoma, Non-Small-Cell LungFluorescent Antibody TechniqueImmune Checkpoint InhibitorsLung NeoplasmsDeep LearningHumansImmunotherapyMultivariate AnalysisProgression-Free SurvivalTumor MicroenvironmentImmune Checkpoint Inhibitors

Identifiers

PMID41634004
PMCPMC12868679

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.