Rupatadine-inhibited OTUD3 promotes DLBCL progression and immune evasion through deubiquitinating MYL12A and PD-L1

Autor: Ying Sui, Ziyang Shen, Xiaoyou Li, Ya Lu, SiTong Feng, Rong Ma, Jianzhong Wu, Changwen Jing, Zhuo Wang, Jifeng Feng, Haixia Cao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Death and Disease, Vol 15, Iss 8, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-024-06941-x
Popis: Abstract The obstacle to effectively treating Diffuse Large B-cell Lymphoma (DLBCL) lies in the resistance observed toward standard therapies. Identifying therapeutic targets that prove effective for relapsed or refractory patients poses a significant challenge. OTUD3, a deubiquitinase enzyme, is overexpressed in DLBCL tissues. However, its role in DLBCL has not been investigated. Our study has brought to light the multifaceted impact of OTUD3 in DLBCL. Not only does it enhance cell survival through the deubiquitination of MYL12A, but it also induces CD8+ T cell exhaustion within the local environment by deubiquitinating PD-L1. Our findings indicate that the OTUD3 inhibitor, Rupatadine, exerts its influence through competitive binding with OTUD3. This operation diminishes the deubiquitination of both MYL12A and PD-L1 by OTUD3. This research unveils the central and oncogenic role of OTUD3 in DLBCL and highlights the potential clinical application value of the OTUD3 inhibitor, Rupatadine. These findings contribute valuable insights into addressing the challenges of resistant DLBCL cases and offer a promising avenue for further clinical exploration.
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