Sperm-specific proteins and cancer testis antigens exist outside the blood-testis barrier

Sperm develop in the seminiferous tubules of the testis from puberty, sequestered inside the blood-testis barrier to prevent their recognition as “non-self” by the immune system. It is widely assumed that proteins expressed specifically in sperm do not have direct access to the circulation or the immune system. This assumption underlies the pursuit of cancer testis antigens (CTAs) as therapeutic targets and biomarkers for particular cancers. CTAs are aberrantly expressed in cancer but only expressed in sperm in healthy men; thus these proteins are assumed to be absent from the blood and/or to be neoantigens.