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Interleukin-10 receptor signaling promotes the maintenance of a PD-1int TCF-1+ CD8+ T cell population that sustains anti-tumor immunity

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

ORGANISM(S): Mus musculus

PROVIDER: GSE102602 | GEO | 2021/12/08

REPOSITORIES: GEO

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Interleukin-10 receptor signaling promotes the maintenance of a PD-1int TCF-1+ CD8+ T cell population that sustains anti-tumor immunity

Project description:Interleukin-10 receptor signaling promotes the maintenance of a PD-1int TCF-1+ CD8+ T cell population that sustains anti-tumor immunity

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Metabolic Reprogramming of Terminally Exhausted CD8+ T-cells by Interleukin-10 Enhances Anti-Tumour Immunity

Project description:Terminally exhausted CD8+ T-cells, which hold certain level of anti-tumour cytotoxicity but largely reduced proliferation capacity, contribute directly to tumour growth control. However, this subpopulation do not respond to immune checkpoint blockades or most existing immunotherapies and are difficult to be reactivated. Here, we show that a half-life extended interleukin (IL)-10/Fc fusion protein directly expands the terminally exhausted CD8+ TILs and sustains their effector functions through in vivo metabolic reprogramming, leading to eradication of established solid tumours and durable cures in a majority of treated mice when combined with adoptive T-cell transfer immunotherapy. Our results provide preclinical evidence that IL-10/Fc is a safe and highly effective therapy that acts on a specific subset of CD8+ TILs distinct from those responding to immune checkpoint blockades. Thus, IL-10/Fc could complement and synergize with existing cancer immunotherapies for enhanced efficacy and response rates. We find that IL-10/Fc reprograms T-cell metabolism by promoting oxidative phosphorylation through the mitochondrial pyruvate carrier, suggesting that metabolic reprogramming is sufficient to revitalize terminally exhausted CD8+ TILs.

2021-04-01 | GSE168990 | GEO