ArticleNature communications2025
Resistance to anti-LAG-3 plus anti-PD-1 therapy in head and neck cancer is mediated by Sox9+ tumor cells interaction with Fpr1+ neutrophils.
Article in Nature communications, 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 8 papers.
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.
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.
Who cites it
8 citing papers in PubMed.
- Optimizing immunotherapy for head and neck squamous cell carcinoma: recent advances and future directions.Annals of medicine · 2026Review
- γδ T cells and cancer.The Journal of clinical investigation · 2026Review
- GM-CSF Promotes Neutrophil PD-L1 Expression Through the VEGFR-2/STAT6/CSF2 Signaling Axis in Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Regulation of acute myocardial infarction by CircTMCC1 through mitochondrial dysfunction and AMPK/mTOR-driven M1 macrophage polarization: role in QFR assessment.Cell death discovery · 2026Article
- Neutrophil Heterogeneity: Molecules to Cellular Behavior.Life (Basel, Switzerland) · 2026Review
- Mitophagy-driven immune evasion in skin cancer: multidimensional regulatory networks and context-dependent therapeutic strategies-a narrative review.Frontiers in immunology · 2026Review
- A Trojan horse nanoplatform overcoming delivery barriers for targeted gene immunotherapy of colorectal cancer.Frontiers in bioengineering and biotechnology · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors.
Funding
Abstract
Relatlimab and nivolumab combination therapy shows significant efficacy in treating various types of cancer. Current research on the molecular mechanisms of this treatment is abundant, but in-depth investigations into post-treatment resistance remain notably lacking. In this study, we identify significant enrichment of SRY (sex determining region Y)-box 9 (Sox9)+ tumor cells in resistant samples using single cell RNA sequencing (scRNAseq) in a head and neck squamous cell carcinoma (HNSCC) mouse model. In addition, Sox9 directly regulates the expression of annexin A1 (Anxa1), mediating apoptosis of formyl peptide receptor 1 (Fpr1)+ neutrophils through the Anxa1-Fpr1 axis, which promotes mitochondrial fission, inhibits mitophagy by downregulating BCL2/adenovirus E1B interacting protein 3 (Bnip3) expression and ultimately prevents the accumulation of neutrophils in tumor tissues. The reduction of Fpr1+ neutrophils impairs the infiltration and tumor cell-killing ability of cytotoxic Cd8 T and γδT cells within the tumor microenvironment, thereby leading to the development of resistance to the combination therapy. We further validate these findings using various transgenic mouse models. Overall, this study comprehensively explains the mechanisms underlying resistance to the anti-LAG-3 plus anti-PD-1 combination therapy and identifies potential therapeutic targets to overcome this resistance.
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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.