| Autor: |
Fisher KE; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas. kevin.fisher@bcm.edu., Ferguson LS; Department of Pathology, Texas Children's Hospital, Houston, Texas., Coffey AM; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas, USA; Clinical Pathology Associates, Austin, Texas., Merritt BY; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas., Curry JL; Department of Pathology and Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas., Marcogliese AN; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas., Major AM; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas., Kamdar KY; Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer and Hematology Centers, Houston, Texas., Lopez-Terrada DH; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas, USA; Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer and Hematology Centers, Houston, Texas., Curry CV; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas. ccurry@bcm.edu. |
| Abstrakt: |
Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are immunomodulatory molecules overexpressed in lymphomas and are promising immunotherapy targets for hematologic malignancies. However, studies of PD-1/PD-L1 overexpression and their clinical significance in aggressive pediatric non-Hodgkin lymphomas (NHL) are limited. We assessed PD-1/PD-L1 overexpression using immunohistochemistry in 68 aggressive pediatric NHL: ALK-positive anaplastic large cell lymphoma (ALK+ ALCL, n=8), Burkitt lymphoma (BL, n=27), and large B-cell lymphoma (LBCL) de novo LBCL, n=22 and diffuse LBCL arising as monomorphic post-transplant lymphoproliferative disorder [PTLD-DLBCL], n=11. In LBCL, correlations between PD-L1 overexpression and Epstein-Barr virus (EBV) status, cell of origin, stage, nodal status, overall survival (OS), and event-free survival (EFS) were examined. The genetic mechanisms of PD-L1 overexpression were investigated using targeted next-generation sequencing (NGS) and cytogenetic data. All ALK+ ALCL samples, 50.0% of de novo LBCL (11/22), 72.7% of PTLD-DLBCL (8/11), and no BL overexpressed PD-L1. Overexpressed PD-L1 correlated with EBV positivity (P=0.033) in LBCL and lower EFS in de novo LBCL (P=0.017). NGS of select LBCL revealed distinct somatic mutations and an ultra-hypermutated PTLD-DLBCL. Most cases with 9p24.1 copy gains overexpressed PD-L1 although some cases had no discernible genetic drivers of PD-L1 overexpression. Overexpressed PD-L1 is common in pediatric LBCL, associated with EBV positivity and 9p24.1 gains, and may have prognostic significance in de novo LBCL. Furthermore, diverse molecular mechanisms for PD-L1 overexpression in aggressive pediatric NHL can occur. Thus, additional studies exploring the therapeutic and prognostic significance and molecular mechanisms of PD-L1 overexpression in aggressive pediatric NHL are warranted. |
