Retroviral glycoprotein-mediated immune suppression via the potassium channel KCa3.1 – A new strategy for amelioration of inflammatory bowel diseases

Laska, Magdalena Janina; Møller, Jesper Bonnet; Graversen, Jonas Heilskov; Strøbæk, Dorte; Blomster, Linda V.; Christophersen, Palle; Bahrami, Shervin

doi:10.1016/j.clim.2022.109081

Cited by 2 publications

(2 citation statements)

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“…We found that the HERV-W ISDwt vaccine generated significantly higher CD8 + and CD4 + T-cell responses to certain regions of the Env protein than the HERV-W ISDrev vaccine, indicating that the effects of the mutations are not solely structural or sequence dependent. While our study did not uncover the immune regulatory mechanisms of the ISD or address the potential direct involvement with the KCa3.1 potassium channels reported by Laska et al [ 38 ], it does support the previously published study by Mangeney et al and the general “ISD hypothesis” [ 30 ].…”

Section: Discussionsupporting

confidence: 77%

“…This controversy highlights that the mechanism of (H)ERV ISDs is not fully understood. A recent study proposed a direct role of the (H)ERV ISD, as they found that an ISD peptide from the HERV family, HERV-H, exhibited immunosuppressive properties and direct antagonistic effects on the potassium channel KCa3.1, which is normally required for the maturation of APC and T-cell responses [ 38 ]. However, it is yet unclear how this ISD peptide would interact with KCa3.1 when part of a full-length Env protein.…”

Section: Introductionmentioning

confidence: 99%

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Human Ad19a/64 HERV-W Vaccines Uncover Immunosuppression Domain-Dependent T-Cell Response Differences in Inbred Mice

Skandorff

Ragonnaud

Gille

et al. 2023

IJMS

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Expression of human endogenous retrovirus type W (HERV-W) has been linked to cancer, making HERV-W antigens potential targets for therapeutic cancer vaccines. In a previous study, we effectively treated established tumours in mice by using adenoviral-vectored vaccines targeting the murine endogenous retrovirus envelope and group-specific antigen (Gag) of melanoma-associated retrovirus (MelARV) in combination with anti-PD-1. To break the immunological tolerance to MelARV, we mutated the immunosuppressive domain (ISD) of the MelARV envelope. However, reports on the immunogenicity of the HERV-W envelope, Syncytin-1, and its ISD are conflicting. To identify the most effective HERV-W cancer vaccine candidate, we evaluated the immunogenicity of vaccines encoding either the wild-type or mutated HERV-W envelope ISD in vitro and in vivo. Here, we show that the wild-type HERV-W vaccine generated higher activation of murine antigen-presenting cells and higher specific T-cell responses than the ISD-mutated counterpart. We also found that the wild-type HERV-W vaccine was sufficient to increase the probability of survival in mice subjected to HERV-W envelope-expressing tumours compared to a control vaccine. These findings provide the foundation for developing a therapeutic cancer vaccine targeting HERV-W-positive cancers in humans.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%