ArticleMolecular therapy. Nucleic acids2021
Association of clock-like mutational signature with immune checkpoint inhibitor outcome in patients with melanoma and NSCLC.
Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Five dominant amino acid substitution signatures shape tumour immunity.Molecular systems biology · 2026Article
- Comprehensive analysis of mutational processes across 20 000 adult and pediatric tumors.Nucleic acids research · 2025Article
- Novel prognostic biomarkers in small cell lung cancer reveal mutational signatures, genomic mutations, and immune implications.Scientific reports · 2025Article
- A mutational signature and ARID1A mutation associated with outcome in hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma.Frontiers in genetics · 2025Article
- Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non-Small Cell Lung Cancer.Cancer research · 2024Article
- Topography of mutational signatures in non-small cell lung cancer: emerging concepts, clinical applications, and limitations.The oncologist · 2024Review
- Tumour mutational burden: clinical utility, challenges and emerging improvements.Nature reviews. Clinical oncology · 2024Review
- Prognostic and immune correlation analysis of mitochondrial autophagy and aging-related genes in lung adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- Clock-like Mutation Signature May Be Prognostic for Worse Survival Than Signatures of UV Damage in Cutaneous Melanoma.Cancers · 2023Article
- Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome.NPJ genomic medicine · 2023Article
- CLOCK'ing differences in DNA methylation signatures to understand the molecular etiology of lung cancer.Translational lung cancer research · 2023Article
- Using genomic scars to select immunotherapy beneficiaries in advanced non-small cell lung cancer.Scientific reports · 2023Article
- Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy.Journal for immunotherapy of cancer · 2023Article
- Unveiling the interplay between mutational signatures and tumor microenvironment: a pan-cancer analysis.Frontiers in immunology · 2023Article
- Prognostic biomarkers correlated with immune infiltration in non-small cell lung cancer.FEBS open bio · 2023Article
- Distinct non-clock-like signatures of the basal cell carcinomas from three sisters with a lethal Gorlin-Goltz syndrome.BMC medical genomics · 2022Article
- Mutation burden-orthogonal tumor genomic subtypes delineate responses to immune checkpoint therapy.Journal for immunotherapy of cancer · 2022Article
- Deciphering the tumor microenvironment cell-infiltrating landscape reveals microenvironment subtypes and therapeutic potentials for nonsquamous NSCLC.JCI insight · 2022Article
- Shared genetic and epigenetic changes link aging and cancer.Trends in cell biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitor (ICI) therapy has achieved remarkable clinical benefit in melanoma and non-small cell lung cancer (NSCLC). Tumor mutational signatures are the fingerprints of endogenous and exogenous factors that have acted throughout tumorigenesis and heterogeneity; however, their association with immune response in ICI-treated samples remains unclear. Here, we leveraged whole-exome sequencing (WES)-based mutational profiles combined with clinicopathologic characteristics from melanoma and NSCLC datasets to examine whether tumor genomic features contribute to clinical benefit of ICI treatment. Mutational data acquired from targeted next-generation sequencing (NGS) assays (MSK-IMPACT panels) were also employed for further corroboration. A mutational signature (known as age-related clock-like processing) characterized by enrichment of C>T mutations at NpCpG trinucleotides were identified to be associated with a worse prognosis and lower tumor mutation load (TML) in both WES and targeted NGS immunotherapy cohorts. We also analyzed gene transcriptomic profiles and identified immune regulation-related gene pathways that were significantly altered in samples with different clock-like signature grouping. Leucocyte subset analysis further revealed that clock-like signature was associated with the reduction of cytotoxic cell infiltration and elevation of regulatory T cells. Overall, our work re-annotated that the age-related clock-like signature was associated with worse prognosis and lower immune activity, offering opportunities to stratify patients into optimal immunotherapy plans based on genomic subtyping.
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