title: PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.
abstract: Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.
authors.affiliation: Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.affiliation: Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Dresser
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.affiliation: Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.|Present Address: Department of Pathology and Laboratory Medicine, VA Boston Healthcare System, West Roxbury, MA, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Woda
authors.affiliation: Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor
keywords: diffuse large B-cell lymphoma; immune checkpoint; immunotherapy; programmed cell death ligand 1