Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs)

J Immunother Cancer. 2021 May;9(5):e002694. doi: 10.1136/jitc-2021-002694.

Abstract

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+ T cell responses which possibly drive the fate of cancer development and progression.

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.

Keywords: CD8-positive T-lymphocytes; antigens; cellular; immunity; immunotherapy; vaccination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • 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*
  • Memory T Cells / metabolism
  • Memory T Cells / virology
  • Models, Immunological
  • Protein Conformation
  • Sequence Homology, Amino Acid

Substances

  • Antigens, Neoplasm
  • Antigens, Viral
  • Epitopes
  • IFNG protein, human
  • Interferon-gamma