PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies.

Abstract

PURPOSE Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed-Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors. EXPERIMENTAL DESIGN Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1. RESULTS Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1. CONCLUSION Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies.

DOI: 10.1158/1078-0432.CCR-13-0855

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@article{Chen2013PDL1EI, title={PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies.}, author={Benjamin J. Chen and Bjoern Chapuy and Jing Ouyang and Heather H. Sun and Margaretha G.M. Roemer and Mina LuQing Xu and Hongbo Yu and Christopher D. M. Fletcher and Gordon J Freeman and Margaret A. Shipp and Scott J. Rodig}, journal={Clinical cancer research : an official journal of the American Association for Cancer Research}, year={2013}, volume={19 13}, pages={3462-73} }