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TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE169715 | GEO | 2022/02/22

REPOSITORIES: GEO

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TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment

Project description: Not available

| S-SCDT-EMBOR-2021-52984V1 | biostudies-other

TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment I

Project description:Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observed that expression of telomerase reverse transcriptase (TERT) is closely associated with immune-suppressive signatures. We demonstrated that TERT can activate a subclass of endogenous retroviruses (ERVs) to form double-stranded RNAs (dsRNAs), which were sensed by the RIG-1/MDA5-MAVS signalling pathway and triggered interferon signalling in cancer cells. Furthermore, we showed that TERT-induced ERVs/interferon signalling stimulated the expression of chemokines, including CXCL10, which induced suppressed T cell infiltration with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERVs/interferon signalling contributes to immune suppression in tumours.

2022-02-22 | GSE169711 | GEO

TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment III

2022-02-22 | GSE169714 | GEO

TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment II

2022-02-22 | GSE169713 | GEO