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DDX10 Exacerbates Exosomal PD-L1-Dependent T Cell Exhaustion via Phase Separation of Rab27b in Oral Squamous Cell Carcinoma.

Bowen Li | Hao Cui | Wei Liu | Zhou Lan | Chang Liu | Yumiao Yang | Yuyue Zhao | Zhen Tian | Hao Chen | Guangtao Yu
Research (Washington, D.C.) | 2025

DEAD-box ATPase 10 (DDX10), a prominent RNA-binding protein in the DDX family, has a critical function in cancer progression. Nevertheless, its well-defined mechanisms in oral squamous cell carcinoma (OSCC) are still not well understood. Here, we identify that DDX10 is substantially increased in OSCC, which is positively correlated with poor prognosis and malignant behavior. Mechanistically, we found that DDX10 had physical interaction with Rab27b by undergoing phase separation. Knockdown of DDX10 inhibited Rab27b-mediated exosome secretion and the expression of programmed cell death-ligand 1 (PD-L1) within its contents. Furthermore, knocking down DDX10 could restore the function and infiltration of T cells, hence inhibiting the progression of OSCC. These findings highlight that the oncogenic role of DDX10 in promoting exosomal PD-L1 secretion via phase separation with Rab27b has been preliminarily validated in T cell exhaustion in OSCC. A potential strategy for improving OSCC immunotherapy may involve the inhibition of DDX10.

Pubmed ID: 40352946

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PhaSePred (tool)

RRID:SCR_024969

Web server as meta-predictor for phase-separating proteins. Displays proteome-level quantiles of different features, thus profiling PS propensity and providing crucial information for identification of candidate proteins.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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