Background The host’s immune system develops in equilibrium with both cellular self-antigens and non-self antigens derived from microorganisms (e.g. viruses and microbiota) 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). Here we offer a new perspective, proposing that a molecular mimicry between the two classes of non-self antigens may play a role in cancer development and progression.

Methods In the present study we looked for homology between published TAAs and non-self microorganism-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed.

Results Several of such homologies have been found. Moreover, structural similarities between paired TAAs and microorganism peptides as well as comparable patterns of contact with HLA and TCR α and β chains have been observed. Moreover, cross-reacting T cells have been identified by tetramer and IFN-γ ELISpot assays.

Conclusions The two classes of non-self antigens may converge, eliciting cross-reacting CD8+ T cell responses which possibly drive the fate of cancer development and progression. An established anti-microorganism T cell memory may turn out to be an anti-cancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the microorganism-derived epitope. This may ultimately represent a relevant selective advantage for cancer patients and may lead to a novel preventive anti-cancer vaccine strategy.

Disclosure Information L. Buonaguro: None.