Oncotarget

Research Papers:

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications

Wei Xing, Karen Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda and Benjamin J. Chen _

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Oncotarget. 2016; 7:59976-59986. https://doi.org/10.18632/oncotarget.11045

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Abstract

Wei Xing1, Karen Dresser1, Rui Zhang2, Andrew M. Evens3, Hongbo Yu1,4, Bruce A. Woda1, Benjamin J. Chen1

1Department of Pathology, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA

2Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

3Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, USA

4Present Address: Department of Pathology and Laboratory Medicine, VA Boston Healthcare System, West Roxbury, MA, USA

Correspondence to:

Benjamin J. Chen, email: benjamin.chen@umassmemorial.org

Keywords: programmed cell death ligand 1, diffuse large B-cell lymphoma, immune checkpoint, immunotherapy

Received: December 28, 2015     Accepted: July 18, 2016     Published: August 04, 2016

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.


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