In:
The EMBO Journal, EMBO, Vol. 41, No. 16 ( 2022-08-16)
Abstract:
image TGF‐β signaling is a key factor in tumor progression and is associated with poor response to cancer immunotherapy. This work shows that pharmacologically targeting the deubiquitinase USP8 can antagonise TGF‐β/SMAD signalling and improve the efficacy of cancer immunotherapy USP8 is a metastasis enhancer that directly deubiquitinates and stabilises TGF‐β receptor TβRII, thereby promoting TGF‐β/SMAD signaling. Gain of USP8 function promotes the secretion of TβRII+ circulating extracellular vesicles that induce CD8+ T cell exhaustion. Pharmacological inhibition of USP8 represses TGF‐β signalling and inhibits cancer progression. USP8 inhibition alleviates CD8+ T cell exhaustion and improves the efficacy of breast cancer immunotherapy.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.2021108791
Language:
English
Publisher:
EMBO
Publication Date:
2022
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12