Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).
Concetta Ragone, Carmen Manolio, Beatrice Cavalluzzo, Angela Mauriello, Maria Lina Tornesello, Luigi Buonaguro, Filippo Castiglione, Luigi Vitagliano, Emanuela Iaccarino, Menotti Ruvo, Maria Tagliamonte, Luigi Buonaguro
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.