Cause and consequence of cancer/testis antigen activation in cancer

Tumor cells frequently exhibit widespread epigenetic aberrations that significantly alter the repertoire of expressed proteins. In particular, it has been known for nearly 25 years that tumors frequently reactivate genes whose expression is typically restricted to germ cells. These gene products are classified as cancer/testis antigens (CTAs) owing to their biased expression pattern and their immunogenicity in cancer patients. While these genes have been pursued as targets for anticancer vaccines, whether these reactivated testis proteins have roles in supporting tumorigenic features is less studied. Recent evidence now indicates that these proteins can be directly employed by the tumor cell regulatory environment to support cell-autonomous behaviors. Here, we review the history of the CTA field and present recent findings indicating that CTAs can play functional roles in supporting tumorigenesis.