PT  - JOURNAL ARTICLE
AU  - Andorsky, David J.
AU  - Yamada, Reiko E.
AU  - Said, Jonathan
AU  - Pinkus, Geraldine S.
AU  - Betting, David J.
AU  - Timmerman, John M.
TI  - Programmed Death Ligand 1 Is Expressed by Non–Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells
AID  - 10.1158/1078-0432.CCR-10-2660
DP  - 2011 Jul 01
TA  - Clinical Cancer Research
PG  - 4232--4244
VI  - 17
IP  - 13
4099  - http://clincancerres.aacrjournals.org/content/17/13/4232.short
4100  - http://clincancerres.aacrjournals.org/content/17/13/4232.full
SO  - Clin Cancer Res2011 Jul 01; 17
AB  - 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.