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Quantifying immune-based counterselection of somatic mutations
- Source :
- PLoS Genetics, Vol 15, Iss 7, p e1008227 (2019), PLoS Genetics
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- Somatic mutations in protein-coding regions can generate ‘neoantigens’ causing developing cancers to be eliminated by the immune system. Quantitative estimates of the strength of this counterselection phenomenon have been lacking. We quantified the extent to which somatic mutations are depleted in peptides that are predicted to be displayed by major histocompatibility complex (MHC) class I proteins. The extent of this depletion depended on expression level of the neoantigenic gene, and on whether the patient had one or two MHC-encoding alleles that can display the peptide, suggesting MHC-encoding alleles are incompletely dominant. This study provides an initial quantitative understanding of counter-selection of identifiable subclasses of neoantigenic somatic variation.<br />Author summary Cancer immunotherapy and personalized cancer vaccines depend on clearance of cancer and pre-cancer cells by the immune system. However, little is known about the strength of this phenomenon as it acts on the cell populations which give rise to tumors. Here we provide an initial quantitative estimate of the fraction of neo-antigen-containing cells in this population that are cleared by the MHC class I-dependent immune system. The impacts of both neo-antigenic gene expression and the number of neo-antigen-displaying MHC alleles on this clearance phenomenon were examined. A more complete understanding of immune clearance of neoantigenic cells and how this phenomenon varies between patients and cancers, has the potential to guide immunotherapy and cancer vaccines.
- Subjects :
- Cancer Research
Physiology
Somatic cell
medicine.medical_treatment
Protein Expression
Gene Expression
QH426-470
medicine.disease_cause
Biochemistry
Major Histocompatibility Complex
0302 clinical medicine
Immune Physiology
Medicine and Health Sciences
Genetics (clinical)
Genetics
Antigen Presentation
0303 health sciences
Mutation
Immune System Proteins
biology
integumentary system
3. Good health
Gene types
Immune selection
030220 oncology & carcinogenesis
Research Article
Immunology
Antigen presentation
Mutation, Missense
MHC class I genes
Research and Analysis Methods
Major histocompatibility complex
03 medical and health sciences
Immune system
Germline mutation
Antigen
Antigens, Neoplasm
Gene Expression and Vector Techniques
medicine
Humans
Antigens
Allele
Molecular Biology Techniques
Molecular Biology
Gene
Alleles
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
Molecular Biology Assays and Analysis Techniques
Histocompatibility Antigens Class I
MHC Class I Gene
Biology and Life Sciences
Proteins
Cancer
Immunotherapy
medicine.disease
Genetic Loci
biology.protein
Somatic Mutation
Clinical Immunology
Clinical Medicine
Peptides
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 15
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....4469f0a7690dfc785f0beb4f6dc4cdfe