PD-L1 Expression is Characteristic of a Subset of Aggressive B-Cell Lymphomas and Virus-Associated Malignancies
By Benjamin J Chen, B. Chapuy, Ouyang Jing, Heather H. Sun, M. Roemer, Mina L. Xu, Hongbo Yu, C. Fletcher, G. Freeman, M. Shipp and 1 more. Clinical Cancer Research, 2013
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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. Clin Cancer Res; 19(13); 3462–73. ©2013 AACR.
Subfields: Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/06074f028bf5d1542e05cdc0a99736952d94a038
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Citations in the corpus
- PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. (2016, neutral): “Age, years Median (range) 30 (18-69) 30 (18-56) 29 (18-66) 29 (19-69) Stage, No.”
- PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy (2015, background): “Flow cytometric measurement of PD-L1 expressionhasbeenutilized, and a general trend towards increased PD-L1 expression on virally mediated hematologic cancers is apparent (27).”
- Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. (2016, background): “Lipase increased 3 (4) 1 (1) Mucosal inflammation 3 (4) 1 (1) Stomatitis 2 (2) 1 (1) Diplopia 1 (1) 1 (1) Pneumonia 1 (1) 1 (1) Pulmonary embolism 1 (1) 1 (1) Rash pustular 1 (1) 1 (1) Sepsis 1 (1) 1 (1) ARDS† 1 (1) 1 (1) Hematologic Anemia 5 (6) 3 (4) Leukopenia 4 (5) 3 (4) Lymphopenia 3 (4) 1 (1) ”