ArticleNature cancer2024
Tissue-specific thresholds of mutation burden associated with anti-PD-1/L1 therapy benefit and prognosis in microsatellite-stable cancers.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Neoadjuvant chemoradiotherapy with or without PD-1 inhibitors in MMR-proficient non-metastatic rectal cancer: a meta-analysis of randomized controlled trials.Frontiers in immunology · 2026Pooled it
- Trial
- Chronic interferon signaling at baseline is associated with acquired resistance to immunotherapy in metastatic melanoma.Cell reports. Medicine · 2026Article
- A Circulating GPNMB-Based Multimodal Model Integrates Tumor-Immune Crosstalk to Predict Immunotherapy Response in Esophageal Cancer.Cancer discovery · 2026Article
- The Oncology Research Information Exchange Network (ORIEN) - Building a Real-World Collaborative, Patient-driven Infrastructure for Discovery Research and Precision Oncology.Research square · 2026Article
- Article
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Very High vs. High Tumor Mutational Burden Across Tumors: Real-World Associations with MSI, Pathway Features, and Immunotherapy Outcomes.Biomedicines · 2026Article
- Advances and challenges in immunotherapy for advanced esophageal squamous cell carcinoma.Frontiers in immunology · 2026Review
- Aberrant cytoplasmic localization of MLH1 characterizes a cell population that seeds breast cancer recurrence.Nature communications · 2025Article
- Systemic inflammation biomarkers can identify high tumor mutation burden in lung adenocarcinoma.BMC cancer · 2025Article
- Tamoxifen induces PI3K activation in uterine cancer.Nature genetics · 2025Article
- Article
- Facts and Hopes: Toward the Next Quantum Leap in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Authors response to "Letter to the Editor": "Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types".Journal for immunotherapy of cancer · 2025Article
- DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Evaluation of the efficacy and safety of neoadjuvant immunotherapy in locally advanced esophageal squamous cell carcinoma.Journal of thoracic disease · 2025Article
- Comment on 'Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types'.Journal for immunotherapy of cancer · 2025Article
- Real-world evidence provides clinical insights into tissue-agnostic therapeutic approvals.Nature communications · 2025Article
- Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types.Journal for immunotherapy of cancer · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 or its ligand (PD-1/L1) have expanded the treatment landscape against cancers but are effective in only a subset of patients. Tumor mutation burden (TMB) is postulated to be a generic determinant of ICI-dependent tumor rejection. Here we describe the association between TMB and survival outcomes among microsatellite-stable cancers in a real-world clinicogenomic cohort consisting of 70,698 patients distributed across 27 histologies. TMB was associated with survival benefit or detriment depending on tissue and treatment context, with eight cancer types demonstrating a specific association between TMB and improved outcomes upon treatment with anti-PD-1/L1 therapies. Survival benefits were noted over a broad range of TMB cutoffs across cancer types, and a dose-dependent relationship between TMB and outcomes was observed in a subset of cancers. These results have implications for the use of cancer-agnostic and universal TMB cutoffs to guide the use of anti-PD-1/L1 therapies, and they underline the importance of tissue context in the development of ICI biomarkers.
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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.