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Human Endogenous Retrovirus K Triggers an Antigen-Specific Immune Response in Breast Cancer Patients

Departments of ¹ Veterinary Sciences and Michale E. Keeling Center for Comparative Medicine and Research, ² Immunology, ³ Melanoma Medical Oncology, ⁴ Breast Medical Oncology, and ⁵ Surgical Oncology, The University of Texas M. D. Anderson Cancer Center; ⁶ The University of Texas Health Science Center at Houston, Houston, Texas; and ⁷ Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama

Requests for reprints: Feng Wang-Johanning, The University of Texas M. D. Anderson Cancer Center, Houston, TX 78602-6621. Phone: 512-321-3991; Fax: 512-332-5218; E-mail: fwangjoh{at}mdanderson.org.

Key Words: HERV-K envelope protein • anti-HERV-K antibody • tumor-associated antigen • cellular immune response • dendritic cell vaccine • breast cancer

Recent evidence indicates that human cancer cells reactivate the expression of latent human endogenous retroviral (HERV) proteins. However, the extent to which cancer patients mount de novo immune responses against expressed HERV elements is unclear. In this study, we determined the extent of HERV-K env expression in human breast cancer (BC) and whether both humoral and cell-mediated immunity against HERV-K can be found in BC patients. We found HERV-K env protein expression in 88% of BC (n = 119) but not in normal breast (n = 76) tissues. ELISA screening assays detected significant titers of anti–HERV-K env IgG in a large proportion of BC patients. T-cell responses against HERV-K were also detected in peripheral blood mononuclear cells (PBMC) from BC patients stimulated with autologous dendritic cells pulsed with HERV-K env SU antigens. These responses included induction of T-cell proliferation (P = 0.0043), IFN- production measured by enzyme-linked immunospot (P < 0.0001), and multiplex cytokine secretion (P = 0.0033). Multiplex cytokine analysis found a T-helper 1 cytokine response, including interleukin (IL)-2 (P = 0.0109), IL-6 (P = 0.0396), IL-8 (P = 0.0169), and IP-10 (P = 0.0045) secretion during in vitro stimulation of BC PBMC with HERV-K antigen. We also found HERV-K–specific CTLs that were capable of lysing target cells expressing HERV-K env protein in BC patients but not in normal female controls without cancer. These findings suggest that retroviral gene products are capable of acting as tumor-associated antigens activating both T-cell and B-cell responses in BC patients. [Cancer Res 2008;68(14):5869–77]

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