American Association for Cancer Research
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Supplementary Methods, Table 1 from Programmed Death Ligand 1 Is Expressed by Non–Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells

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journal contribution
posted on 2023-03-31, 16:23 authored by David J. Andorsky, Reiko E. Yamada, Jonathan Said, Geraldine S. Pinkus, David J. Betting, John M. Timmerman

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Purpose: Programmed death ligand 1 (PD-L1) is expressed on antigen-presenting cells and inhibits activation of T cells through its receptor PD-1. PD-L1 is aberrantly expressed on some epithelial malignancies and Hodgkin lymphomas and may prevent effective host antitumor immunity. The role of PD-L1 in non–Hodgkin lymphomas (NHL) is not well characterized.Experimental Design: PD-L1 expression was analyzed in cell lines and lymphoma specimens by using flow cytometry and immunohistochemistry. Functional activity of PD-L1 was studied by incubating irradiated lymphoma cells with allogeneic T cells with or without anti-PD-L1 blocking antibody; T-cell proliferation and IFN-γ secretion served as measures of T-cell activation. Similar experiments were conducted using cultures of primary lymphoma specimens containing host T cells.Results: PD-L1 was expressed uniformly by anaplastic large cell lymphoma (ALCL) cell lines, but rarely in B-cell NHL, confined to a subset of diffuse large B-cell lymphomas (DLBCL) with activated B-cell features (3 of 28 cell lines and 24% of primary DLBCL). Anti-PD-L1 blocking antibody boosted proliferation and IFN-γ secretion by allogeneic T cells responding to ALCL and DLBCL cells. In autologous cultures of primary ALCL and DLBCL, PD-L1 blockade enhanced secretion of inflammatory cytokines IFN-γ, granulocyte macrophage colony-stimulating factor, interleukin (IL)-1, IL-6, IL-8, IL-13, TNF-α, and macrophage inflammatory protein-1α. In establishing cell lines from an aggressive PD-L1+ mature B-cell lymphoma, we also noted that PD-L1 expression could be lost under certain in vitro culture conditions.Conclusions: PD-L1 may thwart effective antitumor immune responses and represents an attractive target for lymphoma immunotherapy. Clin Cancer Res; 17(13); 4232–44. ©2011 AACR.

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