Human endogenous retroviruses and cancer

María Gonzalez-Cao, Paola Iduma, Niki Karachaliou, Mariacarmela Santarpia, Julià Blanco, Rafael Rosell


Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persistedthroughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because ofepigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described andmany tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainlyHERV-K (HML6) and HERV-K (HML2). Although the causative role of HERVs in cancer is controversial, data from animalmodels demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generatesan immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. Forexample, HERV-K (HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedgedimmunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cellcytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatorydrugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.


HERVs; cancer; interferon; immunotherapy

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