Prostate cancer (PCa) is one of the leading causes of cancer related death in men in the US. Unfortunately, African Americans (AA) have higher incidence (1.6X) and mortality rates (2.3X) compared to Caucasian Americans (CA). This racial disparity is partially explained by differences in environmental factors such as diet and socioeconomic status; however recent data suggest a biological basis of the racial disparity. We have identified differences in anti-tumor immunity, specifically antigen presentation genes by race with CA PCa tumors expressing higher levels of HLA-DMB and -DPA (8-fold and 128-fold respectively) when compared to AA. Expression of these antigen presentation molecules plays a critical role in anti-tumor immunity, which can influence patient progression and outcome. A study in breast cancer recently reported that the presence of estrogen decreases MHC class II expression. The prostate gland is a hormone responsive organ and in PCa the presence of hormones such as estrogen and testosterone influences progression, treatment and outcome. AA patients have been observed to display increased levels of estrogen and the increase of estrogen receptors has been correlated with more aggressive and late stage PCa tumors. Given the influence of estrogen on antigen presentation genes in breast cancer and the role of estrogen in PCa, we hypothesized that estrogen would influence MHC class II expression and play a role in the racial disparity. In order to test this hypothesis, cell lines derived from AA and CA patients were treated with IFN? in the presence and absence of estrogen to observe the influence of estrogen on MHC class II expression. Our results indicate that HLA-DR expression is decreased in the presence of estrogen in one CA derived cell line PC3 and one AA derived cell line (E006AAhT). We have also found that HLA-DM expression is decreased in the presence of estrogen in E006AAhT, but not in PC3 or DU145. We conclude that the racial background may not be a major factor in determining the influence of estrogen in PCa; however, we have been able to demonstrate the influence of estrogen on MHC class II expression in PCa cell lines.