Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).
Amino Acid Sequence
Antigens, Neoplasm
/ chemistry
Antigens, Viral
/ chemistry
Cells, Cultured
Cross Reactions
Databases, Protein
Enzyme-Linked Immunospot Assay
Epitope Mapping
Epitopes
Host-Pathogen Interactions
Humans
Immunologic Memory
Interferon-gamma
/ metabolism
Interferon-gamma Release Tests
Memory T Cells
/ immunology
Models, Immunological
Protein Conformation
Sequence Homology, Amino Acid
CD8-positive T-lymphocytes
antigens
cellular
immunity
immunotherapy
vaccination
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
accepted:
08
05
2021
entrez:
29
5
2021
pubmed:
30
5
2021
medline:
6
1
2022
Statut:
ppublish
Résumé
The host's immune system develops in equilibrium with both cellular self-antigens and non-self-antigens derived from microorganisms which enter the body during lifetime. In addition, during the years, a tumor may arise presenting to the immune system an additional pool of non-self-antigens, namely tumor antigens (tumor-associated antigens, TAAs; tumor-specific antigens, TSAs). In the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed. Surprisingly, several of such homologies have been found. Moreover, structural similarities between paired TAAs and viral peptides as well as comparable patterns of contact with HLA and T cell receptor (TCR) α and β chains have been observed. Therefore, the two classes of non-self-antigens (viral antigens and tumor antigens) may converge, eliciting cross-reacting CD8 An established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.
Sections du résumé
BACKGROUND
The host's immune system develops in equilibrium with both cellular self-antigens and non-self-antigens derived from microorganisms which enter the body during lifetime. In addition, during the years, a tumor may arise presenting to the immune system an additional pool of non-self-antigens, namely tumor antigens (tumor-associated antigens, TAAs; tumor-specific antigens, TSAs).
METHODS
In the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed.
RESULTS
Surprisingly, several of such homologies have been found. Moreover, structural similarities between paired TAAs and viral peptides as well as comparable patterns of contact with HLA and T cell receptor (TCR) α and β chains have been observed. Therefore, the two classes of non-self-antigens (viral antigens and tumor antigens) may converge, eliciting cross-reacting CD8
CONCLUSIONS
An established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.
Identifiants
pubmed: 34049932
pii: jitc-2021-002694
doi: 10.1136/jitc-2021-002694
pmc: PMC8166618
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Antigens, Viral
0
Epitopes
0
IFNG protein, human
0
Interferon-gamma
82115-62-6
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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