ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Development of functional spatial mapping of the tumour immune microenvironment (FuncO:TiME) in advanced melanomas.BJC reports · 2026Article
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
- ICIsc: A Deep Learning Framework for Predicting Immune Checkpoint Inhibitor Response by Integrating scRNA-Seq and Protein Language Models.Bioengineering (Basel, Switzerland) · 2026Article
- Advancing precision immuno-oncology in melanoma: the synergistic convergence of personalized neoantigen vaccines and multi-omics biomarker profiling.Frontiers in immunology · 2026Review
- Apatinib-Induced STAT1/NK axis activation augments PD-1 inhibitor efficacy in advanced Hepatocellular Carcinoma.Scientific reports · 2025Article
- Toward Personalized Response Monitoring in Melanoma Patients Treated with Immunotherapy and Target Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- Review
- Uncovering gene and cellular signatures of immune checkpoint response via machine learning and single-cell RNA-seq.NPJ precision oncology · 2025Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeIFN signaling in the tumor microenvironment is a critical determinant of both response and resistance of cancer to immune checkpoint inhibitors (ICI). We hypothesized that distinct patterns of IFN signaling in melanoma are associated with clinical response or resistance to ICIs. EXPERIMENTAL
designTwo tissue microarrays containing samples from 97 patients with metastatic melanoma who received nivolumab, pembrolizumab, or a combination of ipilimumab and nivolumab at Yale New Haven Hospital between 2011 and 2017 were randomized into discovery and validation cohorts. Samples were stained and visualized using multiplexed immunofluorescence microscopy for STAT1, STAT1 phosphorylated at Y701 (pSTAT1Y701), and PD-L1, and signals were quantified using the automated quantitative analysis method of quantitative immunofluorescence. Treatment response was assessed using RECIST, and overall survival was analyzed. For in vitro studies, human melanoma cell lines were stimulated with IFNγ and IFNβ, and Western blotting was performed.
resultsPretreatment STAT1 levels were higher in responders to ICIs [complete response/partial response/stable disease (SD) for > 6 months] than in nonresponders (SD < 6 months/progressive disease). Higher pretreatment STAT1 levels were associated with improved survival after ICIs in both the discovery and validation cohorts. Western blot analysis of human melanoma cell lines stimulated with IFN demonstrated distinct patterns of upregulation of STAT1 compared with pSTAT1Y701 and PD-L1. When combining STAT1 and PD-L1 markers, patients with STAT1highPD-L1low tumors had improved survival compared with those with STAT1lowPD-L1high tumors.
conclusionsSTAT1 may better predict melanoma response to ICIs than current strategies, and combined STAT1 and PD-L1 biomarkers may provide insight into IFN-responsive versus IFN-resistant states.
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Registered trials
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.