Laminarin suppresses PD-L1 translation by targeting YTHDF1 to exert antitumor immunity in triple-negative breast cancer.

Authors

Fangning Lou, Xiaoya Zhang, Jianuo Fu, Mengyao Liu, Yuan Zhu, Kaixian Chen, Mingyue Zheng, Sulin Zhang

Published in

Pharmacological research. Pages 109665. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

Triple-negative breast cancer (TNBC) is characterized by low response rates and rapid acquired resistance to current immunotherapies, highlighting an urgent unmet clinical need for novel therapeutic strategies. Herein, we demonstrated that laminarin, a biocompatible β-1,3-glucan extracted from brown algae, exerts significant antitumor immune effects against TNBC with no evident toxicity under the tested conditions. In addition, laminarin suppressed pulmonary metastatic progression in a TNBC metastasis model. Via an innovative in silico target screening framework integrating AI-driven knowledge graph-based causal reasoning with transcriptional signature-based pattern matching, we identified the m⁶A reader YTHDF1 as the key functional target of laminarin in TNBC. Clinical data analysis revealed that YTHDF1 is significantly overexpressed in breast cancer, whose high expression correlates with poor prognosis and tumor immune evasion. We further validated that YTHDF1 directly upregulates programmed death-ligand 1 (PD-L1) expression in TNBC cells. Mechanistically, laminarin directly binds to the YTH domain of YTHDF1, disrupts its interaction with m⁶A-modified PD-L1 mRNA to suppress both basal and IFN-γ-induced PD-L1 upregulation at the translational level. In vitro and in vivo experiments confirmed that the antitumor immune efficacy of laminarin is largely YTHDF1-dependent. Our findings uncover a novel mechanism of action of laminarin, by which it modulates the YTHDF1-m⁶A-PD-L1 axis, providing preclinical evidence supporting further investigation of laminarin as a potential immunomodulatory strategy for TNBC.

PMID:
42854998
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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