Division of Hematology & Oncology, Department of Medicine, and Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Clin Cancer Res. 2011 Jul 1;17(13):4232-44. doi: 10.1158/1078-0432.CCR-10-2660. Epub 2011 May 3.
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.
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.
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.
PD-L1 may thwart effective antitumor immune responses and represents an attractive target for lymphoma immunotherapy.
程序性死亡配体 1（PD-L1）在抗原呈递细胞上表达，并通过其受体 PD-1 抑制 T 细胞的激活。PD-L1 在一些上皮恶性肿瘤和霍奇金淋巴瘤中异常表达，可能阻止有效的宿主抗肿瘤免疫。PD-L1 在非霍奇金淋巴瘤（NHL）中的作用尚未得到很好的描述。
通过流式细胞术和免疫组织化学分析细胞系和淋巴瘤标本中的 PD-L1 表达。通过用抗 PD-L1 阻断抗体孵育辐照的淋巴瘤细胞与同种异体 T 细胞，研究 PD-L1 的功能活性；T 细胞增殖和 IFN-γ 分泌作为 T 细胞激活的衡量标准。使用含有宿主 T 细胞的原发性淋巴瘤标本培养进行类似的实验。
间变性大细胞淋巴瘤（ALCL）细胞系均匀表达 PD-L1，但 B 细胞 NHL 很少见，仅限于具有活化 B 细胞特征的弥漫性大 B 细胞淋巴瘤（DLBCL）亚组（28 个细胞系中的 3 个和 24%的原发性 DLBCL）。抗 PD-L1 阻断抗体增强了同种异体 T 细胞对 ALCL 和 DLBCL 细胞的增殖和 IFN-γ 分泌。在原发性 ALCL 和 DLBCL 的自体培养中，PD-L1 阻断增强了促炎细胞因子 IFN-γ、粒细胞巨噬细胞集落刺激因子、白细胞介素（IL）-1、IL-6、IL-8、IL-13、TNF-α 和巨噬细胞炎症蛋白-1α 的分泌。在建立表达 PD-L1（+）成熟 B 细胞淋巴瘤的细胞系时，我们还注意到 PD-L1 表达在某些体外培养条件下可能丢失。
PD-L1 可能阻碍有效的抗肿瘤免疫反应，是淋巴瘤免疫治疗的一个有吸引力的靶点。
