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Primary mediastinal large B-cell lymphoma (PMBCL) features frequent 9p24.1 genetic alterations driving overexpression of PD-1 ligands PD-L1 and PD-L2. PD-L1 predominantly suppresses Th1 immune signaling and predicts response to PD-1 blockade, while PD-L2 maintains B-cell lineage transcriptional programs and associates with distinct treatment responses. Combined targeting of both ligands enhances Th1 activation and modulates lymphoma transcriptional states.
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