Novel chimeric PD-L1::PD-L2 fusion and immune evasion in lymphoma

Abstract

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.