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Low expression of ALOX15B modulates immunosuppressive tumor microenvironment in diffuse large-B cell lymphoma via the TAP1/MHC-I axis

ABSTRACT: The arachidonic acid (AA) metabolism is closely related to tumor immune evasion and chemo-resistance. ALOX15B (arachidonate 15-lipoxygenase type B), located on chromosome 17p, encodes a key enzyme in AA pathway. Interestingly, the expression of ALOX15B is independent of 17p status but is epigenetically regulated. Low ALOX15B expression predicts poor prognosis, with PGE2 activation and TAP1 suppression, reducing MHC-I expression and creating an immunosuppressive microenvironment. Tucidinostat, a histone deacetylase (HDAC) inhibitor, restores ALOX15B and enhances the TAP1/MHC-I axis, thus promoting lymphoma cell apoptosis, which correlates with the effect of tucidinostat plus immunochemotherapy in a phase II trial of patients with newly diagnosed DLBCL (NCT02753647). Our study provides insight into a novel therapeutic strategy to improve patient prognosis by epigenetically modulating lymphoma metabolism and optimizing the tumor microenvironment.

ORGANISM(S): Mus musculus

PROVIDER: GSE294509 | GEO | 2026/02/18

REPOSITORIES: GEO

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