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Preclinical study reveals that a chimeric PD-L1::PD-L2 fusion drives PD-L1 upregulation in B-cell lymphoma, indicating a novel structural mechanism for immune evasion and immunotherapy selection.
We report a novel in-frame CD274::PDCD1LG2 fusion in primary mediastinal B-cell lymphoma. Functional studies using expression constructs and CRISPR-engineered lymphoma cells confirmed formation of a PD-L1::PD-L2 chimeric protein and marked upregulation of PD-L1 surface expression, consistent with loss of 3′-UTR-mediated repression. These findings expand the genomic landscape of structural mechanisms driving PD-L1 activation and may inform variant interpretation and patient selection for PD-1 blockade in lymphoma.
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Casan et al. (2026) studied this question.
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