Evidence map›Paper›PMID 41291768›Full record

ArticleCancer cell international2025

Circulating IFNγ-associated protein signatures predict response to neoadjuvant immunotherapy in patients with stage III melanoma.

Fei Yang, Su Yin Lim, Ines Pires da Silva, Lijia Yu, Jordan W Conway, Alexander M Menzies, Georgina V Long, Jean Yh Yang, Helen Rizos

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Diagnostics (Basel, Switzerland) · 2026
    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

9 authors.

Fei YangMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Su Yin LimMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Ines Pires da SilvaMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Lijia YuSchool of Mathematics and Statistics, The University of Sydney, Sydney, NSW, Australia.
Jordan W ConwayMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Alexander M MenziesMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Georgina V Long *Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Jean Yh Yang *School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, Australia.
Helen Rizos *Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia. helen.rizos@mq.edu.au.ORCID http://orcid.org/0000-0002-2094-9198

Funding

National Health and Medical Research Council 2012860NHMRC Investigator Grant 2021/GNT2007839NHMRC Investigator Grant APP2017023U.S. Department of Defense FY21 MRP-Team Science Award W81XWH-22-1-0731
6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), have transformed the management of stage III melanoma in the neoadjuvant setting. However, a substantial proportion of patients do not derive benefit from ICI therapy. To improve clinical outcomes, there remains a critical unmet need to identify early biomarkers of response to neoadjuvant immunotherapy in stage III melanoma.

methodsIn this study, we performed longitudinal serum proteomic profiling in 39 patients undergoing neoadjuvant combination anti-PD-1 and anti-CTLA-4 therapy. Using a multiplex proximity extension assay, we measured 702 proteins at three timepoints: baseline, early on-treatment (3-4 weeks after treatment initiation), and pre-surgery (4-8 weeks post-treatment).

resultsThe most pronounced differences between major pathological responders (MPR) and non-MPR patients were detected at baseline and were linked to interferon gamma (IFNγ) signalling, but these differences diminish at later timepoints. A 10-protein IFNγ-associated signature derived from baseline serum profile achieved an AUC of 0.68 for predicting pathological response, comparable to a previously reported tumour-based IFNγ gene signature (AUC = 0.67).

conclusionsThese findings support the use of circulating protein signatures as minimally invasive, scalable biomarkers to inform early treatment decisions in the neoadjuvant setting.

Indexed as

Immune checkpoint inhibitorsMachine learningProteomic profilingProximity extension assaySerum proteins

Identifiers

PMID41291768
PMCPMC12648901

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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.