Abstract 1623: Autoantibodies to human endogenous retrovirus K envelope protein (HERV-K ENV) are associated with features of prostate cancer aggressiveness in African American men

Abstract

Abstract Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in American men. African-American (AA) men are more likely to develop PCa at a younger age and are twice as likely to die from the disease compared to men from other ethnic/racial backgrounds. Even when normalized with equal access to healthcare, socioeconomic status and familial PCa history, AA men still die disproportionately from PCa. Thus, it is paramount to improve the early detection of aggressive PCa. A cancer patient’s humoral immune response to a tumor offers us a minimally invasive opportunity to detect aggressive cancers before a symptomatic tumor emerges. Previous studies indicate that genes associated with immunity and inflammation are significantly upregulated in prostate tumors from AA men compared to European-American (EA) men, suggesting that there are racial differences in the anti-tumor immune response in patients with PCa. This has prompted our laboratory to evaluate the autoantibody repertoire to tumor-associated antigens (TAA) in ethnically diverse patients. Previous studies showed a higher frequency of autoantibodies to the human endogenous retrovirus K (HERV-K) GAG protein in men with late stage PCa. In addition, investigators in this team reported previously an elevated expression of the envelope (ENV) protein in PCa tumors from AA men compared to PCa tumors from EA men. Given the emerging role of HERV-K in human cancers and the potential use of autoantibodies to the ENV and GAG viral proteins as cancer serum biomarkers and immunotherapeutic tools, we investigated the antibody response to the HERV-K ENV in AA and EA men with and without PCa. Using an enzyme-linked immunosorbent assay (ELISA), we detected a significant increase in the frequency of autoantibodies to HERV-K ENV in AA men with PCa compared to EA men with PCa (N=100, p<0.05) and AA men without PCa (N=100, p<0.0001). The frequency of autoantibodies to ENV was also significantly higher in AA men with stage IV (29%, p<0.0001) and AA men with PCa metastasis (40%, p<0.0001) compared to AA men without PCa or EA men with and without PCa. The immunoreactivity of the sera against ENV was confirmed by immunoblotting. To our knowledge this is the first report of an increased autoantibody frequency to HERV-K ENV in PCa patients and the first report of autoantibodies associated with racial differences in PCa. The observation that these autoantibodies are significantly linked to a more aggressive PCa in AA men is also consistent with previous observation of increased upregulation of HERV-K ENV in prostate tumors from AA men. The biological and clinical significance of anti-HERV-K ENV and GAG autoantibodies in PCa, and the racial differences in their frequency and clinical associations, warrant further investigation. Citation Format: Tino W. Sanchez, Shannalee R. Martinez, Greisha Ortiz-Hernandez, Evelyn Sanchez-Hernandez, Christopher Montgomery, Benjamin Becerra, Tiffany Dorsey, Feng Wang-Johanning, Stefan Ambs, Carlos A. Casiano. Autoantibodies to human endogenous retrovirus K envelope protein (HERV-K ENV) are associated with features of prostate cancer aggressiveness in African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1623.