Human endogenous retroviruses and cancer.
Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K (HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are two-edged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.
Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona 08028, Spain.
María
M
Gonzalez-Cao
AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona 08028, Spain.
Paola
P
Iduma
Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona 08028, Spain.
Niki
N
Karachaliou
Medical Oncology Unit, Human Pathology Department, University of Messina, Messina, 98122, Italy.
Mariacarmela
M
Santarpia
AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona 08028, Spain; UVIC-UCC, Catalunya 08500, Spain.
Julià
J
Blanco
Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona 08028, Spain; Cancer Biology & Precision Medicine Program, Catalan Institute of Oncology, Germans Trias I Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, 08916, Spain; Fundación Molecular Oncology Research, Barcelona 08028, Spain.
Rafael
R
Rosell
HERVs; cancer; immunotherapy; interferon