Novel chimeric PD-L1::PD-L2 fusion and immune evasion in lymphoma
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.
Authors
- Fatimah Jalud
- Ing Soo Tiong (ORCID: https://orcid.org/0000-0001-7417-4343)
- Teresa Sadras (ORCID: https://orcid.org/0000-0001-9048-9580)
- Satwica Yerneni (ORCID: https://orcid.org/0000-0003-3709-842X)
- Joshua Casan (ORCID: https://orcid.org/0000-0002-4322-8561)
- Kaitlyn Kew
- Francesca Watts
- Barbara Withers
- Jesse A. Rudd-Schmidt
- Piers Blombery
- Scott A. Williams
Institutions
- The University of Melbourne (AU)
- La Trobe University (AU)
- Peter MacCallum Cancer Centre (AU)
- St Vincent's Hospital Sydney (AU)
- AGRF Ltd (AU)
- Olivia Newton-John Cancer Wellness & Research Centre (AU)
- Olivia Newton-John Cancer Research Institute (AU)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-08-18
- DOI
- https://doi.org/10.1038/s41698-026-01654-0
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00