Cancer-testis antigens (CTAs) represent an expanding class of tumor-associated 
proteins defined on the basis of their tissue-restricted expression to testis or 
ovary germline cells and frequent ectopic expression in tumor tissue. The 
expression of CTA in MHC class I-deficient germline cells makes these proteins 
particularly attractive as immunotherapeutic targets because they serve as 
essentially tumor-specific antigens for MHC class I-restricted CD8+ T cells. 
Moreover, because CTAs are expressed in many types of cancer, any therapeutic 
developed to target these antigens might have efficacy for multiple cancer 
types. Of particular interest among CTAs is the synovial sarcoma X chromosome 
breakpoint (SSX) family of proteins, which includes ten highly homologous family 
members. Expression of SSX proteins in tumor tissues has been associated with 
advanced stages of disease and worse patient prognosis. Additionally, both 
humoral and cell-mediated immune responses to SSX proteins have been 
demonstrated in patients with tumors of varying histological origin, which 
indicates that natural immune responses can be spontaneously generated to these 
antigens in cancer patients. The current review will describe the history and 
identification of this family of proteins, as well as what is known of their 
function, expression in normal and malignant tissues, and immunogenicity.