Cancer Testis Antigens: Not as privileged as once thought.
Cancer testis antigens (CTAs) are a group of proteins linked by proposed importance in cancer immunotherapy. In healthy circumstances, expression of these antigens is restricted to male germ cells in the testis of the adult animal. These ‘antigens’ are assumed to be potentially immunogenic due to the immune-privileged nature of the testis environment, where the adaptive immune system is considered to be excluded. However, during tumorigenesis and cancer development, these antigens are often expressed and have long been considered potential targets for vaccine intervention. Here, O’Donnell et. al. utilise IonOpticks Aurora columns to deeply interrogate the proteome of testicular interstitial fluid and identify a wide range of germ cell‐derived and sperm‐specific proteins. These proteins include multiple CTAs, which appear to be selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules, which lay “outside” the blood‐testis barrier. The results demonstrate a potential for blood‐based tests in the management of male infertility and highlight potential limitations to CTA candidates for cancer immunotherapy given the likelihood of pre-existing immune tolerance due CTA export into the periphery.
Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men. FASEB J. 2021 Mar;35(3):e21397. doi: https://doi.org/10.1096/fj.202002484R.
O'Donnell L, Rebourcet D, Dagley LF, Sgaier R, Infusini G, O'Shaughnessy PJ, Chalmel F, Fietz D, Weidner W, Legrand JMD, Hobbs RM, McLachlan RI, Webb AI, Pilatz A, Diemer T, Smith LB, Stanton PG