Cancer testis antigen expression and immune responses by prostate cancer patients: Implications for prognosis and immunotherapy

Abstract

e16101 Background: Prostate cancer (PC) is the most frequent malignancy in men and it continues to be one of the most common fatal cancers. Treatment options in advanced castration-resistant prostate cancer (CRPC) are limited. Cancer testis (CT) antigens are expressed in a variety of human cancers, but not in normal tissues except for MHC deficient spermatogonia, and represent promising targets for immunotherapy. Little is known about CT antigen expression in relation to disease progression. The aim of this study was to investigate which CT antigens are expressed and immunogenic and hence represent promising targets for patients with prostate cancer and correlate these findings with clinicopathological characteristics. Methods: To determine the expression of 6 CT antigens in prostate cancer immunohistochemistry was performed on tissue micro arrays. We investigated 6 CT antigens (NY-ESO.1, MAGE-C1, MAGE-C2, GAGE, MAGE-A1 and MAGE-A4) in benign hyperplasia (n=45), early (n=388) and late stage (n=71) prostate cancer. To determine the occurrence of spontaneous antibodies against cancer testis antigens, ELISA and Western blot was performed for NY-ESO-1, MAGE-C1 and MAGE-C2 with sera from prostate cancer patients. Results: CT antigens are increasingly expressed in late stage prostate cancers. As an exception we found MAGE-C2 to be expressed early in the course of disease, frequently inducing MAGE-C2 specific antibodies. In later stage metastatic prostate cancer patients NY-ESO-1 is more often expressed, inducing NY-ESO-1 specific antibodies. Conclusions: Cancer testis (CT) antigens are prognostic markers, frequently inducing immune responses and may be suitable for immunotherapeutic intervention in patients with prostate cancer. No significant financial relationships to disclose.