Evidence map›Paper›PMID 41100131›Full record

ArticleJAMA oncology2025

Artificial Intelligence-Detected Tumor-Infiltrating Lymphocytes and Outcomes in Anti-PD-1-Based Treated Melanoma.

Mark Schuiveling, Isabella A J van Duin, Laurens S Ter Maat, Janneke C van der Weerd, Rik J Verheijden, Franchette van den Berkmortel, Christian U Blank, Gerben E Breimer, Femke H Burgers, Marye Boers-Sonderen and 14 more

Erratum issuedAbstract readMulticenter Study
In one paragraph

Article in JAMA oncology, 2025. 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Error in Tables 2 and 3.JAMA oncology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Mark SchuivelingDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Isabella A J van DuinDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Laurens S Ter MaatImage Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Janneke C van der WeerdDepartment of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Rik J VerheijdenDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Franchette van den BerkmortelDepartment of Medical Oncology, Zuyderland Medical Center Sittard, Sittard-Geleen, the Netherlands.
Christian U BlankDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Gerben E BreimerDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Femke H BurgersDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Marye Boers-SonderenDepartment of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
Alfons J M van den EertweghDepartment of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Jan Willem B de GrootIsala Oncology Center, Isala Hospital, Zwolle, the Netherlands.
John B A G HaanenDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Geke A P HospersDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Ellen KapiteijnDepartment of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Djura PiersmaDepartment of Internal Medicine, Medisch Spectrum Twente, Enschede, the Netherlands.
Gerard VreugdenhilDepartment of Internal Medicine, Maxima Medical Center, Eindhoven, the Netherlands.
Hans WestgeestDepartment of Internal Medicine, Amphia Hospital, Breda, the Netherlands.
Anne M R SchraderDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Josien P W PluimMedical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Paul J van DiestDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Mitko VetaMedical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Karijn P M SuijkerbuijkDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Willeke A M BlokxDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Easy and accessible biomarkers associated with response to immune checkpoint inhibition (ICI)-treated melanoma are limited. Objective: To evaluate artificial intelligence (AI)-detected tumor-infiltrating lymphocytes (TILs) on pretreatment melanoma metastases as a biomarker for response and survival in patients treated with ICIs. Design, Setting, and Participants: This multicenter cohort study included patients with advanced melanoma treated with first-line anti-programmed cell death 1 protein (PD-1) with or without anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) between January 2016 and January 2023 at 11 melanoma treatment centers in the Netherlands. Data were analyzed from January to July 2025. Exposure: All patients received first-line anti-PD-1 with or without anti-CTLA-4. Main Outcomes and Measures: The percentage of TILs inside manually annotated tumor area in hematoxylin-eosin-stained pretreatment metastases was determined using the Hover-NeXt model trained and evaluated on an independent melanoma dataset containing 161 835 pathologist-verified manually annotated cells. The primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). Correlation with manual TILs, scored according to the guidelines stated by the Immuno-Oncology Biomarkers Working Group, was evaluated with Spearman correlation coefficients. Logistic regression and Cox proportional regression were conducted, adjusted for age, sex, disease stage, ICI type, BRAF status, brain metastases, lactate dehydrogenase level, and performance status. Results: Of 1202 included patients with advanced cutaneous melanoma, 445 (37.0%) were female and 757 (63.0%) were male, and the median (IQR) age was 67.0 (57.0-74.0) years. The median follow-up was 36.3 months (95% CI, 34.0-39.1). Metastatic melanoma specimens were available for 1202 patients, of whom 423 received combination therapy. The median (range) TIL percentage was 9.9% (0.3%-69.4%). A 10% increase in TILs was associated with increased ORR (adjusted odds ratio, 1.40; 95% CI, 1.23-1.59), PFS (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92), and OS (adjusted hazard ratio, 0.83; 95% CI, 0.76-0.91). Results were consistent for both patients treated with anti-PD-1 monotherapy and patients treated with combination treatment with anti-PD-1 plus anti-CTLA-4. When comparing manual TIL scoring with AI-detected TILs, associations with response and survival were consistently stronger for AI-detected TILs. Conclusions and Relevance: In this cohort study, among patients with advanced melanoma, higher levels of AI-detected TILs on pretreatment hematoxylin-eosin slides were independently associated with improved ICI response and survival. Given the accessibility of TIL scoring on routine histology, TILs may serve as a biomarker for ICI outcomes. To facilitate broader validation, the Hover-NeXt architecture and model weights are publicly available.

Indexed as

Artificial IntelligenceImmune Checkpoint InhibitorsLymphocytes, Tumor-InfiltratingMelanomaProgrammed Cell Death 1 ReceptorSkin NeoplasmsAdultAgedCTLA-4 AntigenFemaleHumansMaleMiddle AgedTreatment OutcomeCTLA-4 AntigenImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID41100131
PMCPMC12532025

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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.