  Numerous epidemiological studies suggest febrile infections could confer
long-term immunity to certain types of cancers, though the precise mechanisms
for this phenomenon remain unclear. Systemic heat-shock responses to fever may
be key to understanding the overlapping outcomes of immune responses to
infection and cancer. To investigate this hypothesis, we performed epitope
discovery between heat-shock proteins (HSP) and cancer-associated antigens
(CAA) and annotated the results with experimentally validated epitopes in the
Immune Epitope Database (IEDB) (Vita et al., 2019). Further, epitopes were
matched with their homologs in human pathogens. Results identified 94 epitopes
shared between HSPs and CAAs, with experimental evidence of presentation at MHC
molecules and with high homology to several epitopes of human pathogens. The
identified epitopes can be used as candidates for designing cancer vaccines.
They may also be used to identify autoreactive antibodies or TCR specificities
that, as antibody drugs and cell therapies, would reproduce the effect of
febrile infection in conferring cancer immunity. Our results support the
hypothesis that the loss of self-tolerance to HSPs during febrile infection
confers tumor immunity through molecular mimicry.
