ArticlePLoS genetics2021
Low immunogenicity of common cancer hot spot mutations resulting in false immunogenic selection signals.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Targeted drug delivery system for ovarian cancer microenvironment: Improving the effects of immunotherapy.Frontiers in immunology · 2022Pooled it
- No evidence of immunosurveillance in mutation-hotspot-driven clonal hematopoiesis.Nature genetics · 2026Article
- Identification of public neoantigens with broad HLA class I coverage as candidates for off-the-shelf cancer vaccine development in colorectal cancer.Frontiers in immunology · 2026Article
- Antigen presentation in cancer - mechanisms and clinical implications for immunotherapy.Nature reviews. Clinical oncology · 2023Review
- Benchmark of tools for in silico prediction of MHC class I and class II genotypes from NGS data.BMC genomics · 2023Article
- Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors.Nature genetics · 2023Article
- Sources of Cancer Neoantigens beyond Single-Nucleotide Variants.International journal of molecular sciences · 2022Review
- Identification of neoantigens for individualized therapeutic cancer vaccines.Nature reviews. Drug discovery · 2022Review
- MHC Class I Deficiency in Solid Tumors and Therapeutic Strategies to Overcome It.International journal of molecular sciences · 2021Review
- Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma.Frontiers in immunology · 2021Article
- Promising New Tools for Targeting p53 Mutant Cancers: Humoral and Cell-Based Immunotherapies.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer is driven by somatic mutations that result in a cellular fitness advantage. This selective advantage is expected to be counterbalanced by the immune system when these driver mutations simultaneously lead to the generation of neoantigens, novel peptides that are presented at the cancer cell membrane via HLA molecules from the MHC complex. The presentability of these peptides is determined by a patient's MHC genotype and it has been suggested that this results in MHC genotype-specific restrictions of the oncogenic mutational landscape. Here, we generated a set of virtual patients, each with an identical and prototypical MHC genotype, and show that the earlier reported HLA affinity differences between observed and unobserved mutations are unrelated to MHC genotype variation. We demonstrate how these differences are secondary to high frequencies of 13 hot spot driver mutations in 6 different genes. Several oncogenic mechanisms were identified that lower the peptides' HLA affinity, including phospho-mimicking substitutions in BRAF, destabilizing tyrosine mutations in TP53 and glycine-rich mutational contexts in the GTP-binding KRAS domain. In line with our earlier findings, our results emphasize that HLA affinity predictions are easily misinterpreted when studying immunogenic selection processes.
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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.