Gastric cancer (GC) is the fourth most common cause of mortality and the fifth for incidence, globally. Diagnosis, early prognosis, and therapy remains challenging for this condition, and new tumor-associated antigens are required for its detection and immunotherapy. Cancer-testis antigens (CTAs) are a subfamily of tumor-associated antigens (TAAs) that have been identified as potential biomarkers and targets for cancer immunotherapy. The CTAs-restricted expression pattern in tumor cells and their potential immunogenicity identify them as attractive target candidates in CTA-based diagnosis or prognosis or immunotherapy. To date, numerous studies have reported the dysregulation of CTAs in GC. Several clinical trials have been done to assess CTA-based immunotherapeutic potential in the treatment of GC patients. NY-ESO-1, MAGE, and KK-LC-1 have been used in GC clinical trials. We review recent studies that have investigated the potential of the CTAs in GC regarding the expression, function, aggressive phenotype, prognosis, and immunological responses as well as their possible clinical significance as immunotherapeutic targets with a focus on challenges and future interventions.

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