ArticleThe Journal of clinical investigation2021
Combined presentation and immunogenicity analysis reveals a recurrent RAS.Q61K neoantigen in melanoma.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Review
- Overcoming T cell tolerance to tumor self-antigens through catch-bond engineering.Science (New York, N.Y.) · 2026Article
- Recurrent Immunogenic Neoantigens and Their Cognate T-cell Receptors in Treatment-Resistant Metastatic Prostate Cancer.Cancer discovery · 2026Article
- Immune landscape of melanoma: Tumor microenvironment, resistance mechanisms, and predictive biomarkers.World journal of clinical oncology · 2026Review
- Prospective tumour mutation burden and neoantigen profiling predicts immunotherapy response in metastatic melanoma.NPJ precision oncology · 2026Article
- Lymphodepleting chemotherapy potentiates neoantigen-directed T cell therapy by enhancing antigen presentation.Cell reports. Medicine · 2025Article
- Enhanced mutanome analysis towards the induction of neoepitope-reactive T-cell responses for personalized immunotherapy of pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- A therapeutic regimen using neoantigen-specific TCR-T cells for HLA-A*2402-positive solid tumors.EMBO molecular medicine · 2025Article
- T-cell receptors identified by a personalized antigen-agnostic screening approach target shared neoantigen KRAS Q61H.Frontiers in immunology · 2025Article
- Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy.Frontiers in immunology · 2025Article
- Structural characterization and AlphaFold modeling of human T cell receptor recognition of NRAS cancer neoantigens.Science advances · 2024Article
- Structural characterization and AlphaFold modeling of human T cell receptor recognition of NRAS cancer neoantigens.bioRxiv : the preprint server for biology · 2024Article
- Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case.Journal for immunotherapy of cancer · 2024Article
- Conformational plasticity of RAS Q61 family of neoepitopes results in distinct features for targeted recognition.Nature communications · 2023Article
- Article
- Large-Scale Immunopeptidome Analysis Reveals Recurrent Posttranslational Splicing of Cancer- and Immune-Associated Genes.Molecular & cellular proteomics : MCP · 2023Article
- Driver mutations inOncoimmunology · 2023Article
- Boosting Antitumor Immunity with an Expanded Neoepitope Landscape.Cancer research · 2022Review
- Effects of Carbon Nanomaterials andPharmaceutics · 2022Review
Corrections and comments
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Authors and funding
31 authors at 13 institutions in 7 countries.
Funding
Abstract
Neoantigens are now recognized drivers of the antitumor immune response. Recurrent neoantigens, shared among groups of patients, have thus become increasingly coveted therapeutic targets. Here, we report on the data-driven identification of a robustly presented, immunogenic neoantigen that is derived from the combination of HLA-A*01:01 and RAS.Q61K. Analysis of large patient cohorts indicated that this combination applies to 3% of patients with melanoma. Using HLA peptidomics, we were able to demonstrate robust endogenous presentation of the neoantigen in 10 tumor samples. We detected specific reactivity to the mutated peptide within tumor-infiltrating lymphocytes (TILs) from 2 unrelated patients, thus confirming its natural immunogenicity. We further investigated the neoantigen-specific clones and their T cell receptors (TCRs) via a combination of TCR sequencing, TCR overexpression, functional assays, and single-cell transcriptomics. Our analysis revealed a diverse repertoire of neoantigen-specific clones with both intra- and interpatient TCR similarities. Moreover, 1 dominant clone proved to cross-react with the highly prevalent RAS.Q61R variant. Transcriptome analysis revealed a high association of TCR clones with specific T cell phenotypes in response to cognate melanoma, with neoantigen-specific cells showing an activated and dysfunctional phenotype. Identification of recurrent neoantigens and their reactive TCRs can promote "off-the-shelf" precision immunotherapies, alleviating limitations of personalized treatments.
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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.