Detection of T Lymphocytes Specific for Human Endogenous Retrovirus K (HERV-K) in Patients with Seminoma

Abstract

Human endogenous retrovirus K (HERV-K) is distinctive among the retroviruses that comprise about 8% of the human genome in that multiple HERV-K proviruses encode full-length viral proteins, and many HERV-K proviruses formed during recent human evolution. HERV-K gag proteins are found in the cytoplasm of primary tumor cells of patients with seminoma. We identified HERV-K-specific T cells in patients with a past history of seminoma using the interferon-gamma ELISPOT assay and an MHC-HERV-K peptide-specific tetramer. A minority of apparently healthy subjects without evident germ cell tumors also made HERV-K-specific T cell responses. In summary, we detected T cell reactivity to HERV-K peptides in both past seminoma patients and a minority of apparently healthy controls.

Prostate Cancer Progression Correlates with Increased Humoral Immune Response to a Human Endogenous Retrovirus GAG Protein

“…Moreover, immune responses to endogenous retrovirus derived proteins have also been correlated to cancer (20,21,23,46), but no clear clinical significance has yet been suggested. Here, we identify an HERV-K GAG protein, located on chromosome 22q11.23, highly expressed in prostate cancer and capable of generating a specific immune response in advanced stages of prostate cancer.…”

“…Specific immune response to endogenous retrovirus components is well described in the field (20,21,23,46), but no clear correlation to cancer progression has yet been determined. In this work, we showed that patients with advanced prostate cancer have a higher incidence of humoral immune response to GAG-HERV-K protein, suggesting an increase in gene expression due to prostate cancer progression.…”

“…15,18,19). Although no expression at the protein level has been clearly identified, immune responses against various HERV components have been widely shown in different types of cancer, including prostate cancer (20)(21)(22)(23)(24). However, a clear correlation between immune response to HERV components and clinical stage has not been intently addressed in prostate cancer.…”

Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells

“…Recently, CTLs recognizing HERV-K-derived peptides that kill tumor cells in vitro have been identified in a few cancer patients (12,14). Similarly, we isolated and expanded a T cell clone from the blood of a responding transplant patient that recognized an HERV-E-derived antigen and killed patient RCC cells and HLA-A11 + RCC cells in vitro.…”

Transposable elements in human cancers by genome-wide EST alignment

“…However, recent studies have revealed that at least some members of the transposable element families are transcriptionally active and may be capable of causing human cancers through several mechanisms. The association of transposable elements with breast cancer (Wang-Johanning et al, 2003b), melanoma (Buscher et al, 2005), seminoma (Rakoff-Nahoum et al, 2006), germ cell tumors (Galli et al, 2005), leukemia (Depil et al, 2002), ovarian carcinomas (Menendez et al, 2004), and prostate adenocarcinoma (Wang-Johanning et al, 2003a) has been suggested. Therefore, transposable elements may play a biological role in cancer development or organismal complexity by introducing transcriptional diversity .…”