Department of Pathology, Kurume University School of Medicine, Kurume, Japan;
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
Blood. 2016 Sep 8;128(10):1374-81. doi: 10.1182/blood-2016-02-698936. Epub 2016 Jul 14.
Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7.4% of patients), and the other showed minimal expression in lymphoma cells (nPD-L1(-), 92.6%). Within the nPD-L1(-) group, 2 subsets emerged: the first displayed abundant PD-L1 expression in nonmalignant stromal cells of the tumor microenvironment (miPD-L1(+), 58.5%) and the second group did not express PD-L1 in any cell (PD-L1(-), 34.1%). nPD-L1(+) ATLL (median survival time [MST] 7.5 months, 95% CI [0.4-22.3]) had inferior overall survival (OS) compared with nPD-L1(-) ATLL (MST 14.5 months, 95% CI [10.1-20.0]) (P = .0085). Among nPD-L1(-) ATLL, miPD-L1(+) ATLL (MST 18.6 months, 95% CI [11.0-38.5]) showed superior OS compared with PD-L1(-) ATLL (MST 10.2 months, 95% CI [8.0-14.7]) (P = .0029). The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P = .0322 and P = .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL.
程序性细胞死亡配体 1（PD-L1）在淋巴恶性肿瘤的肿瘤和肿瘤浸润性非恶性细胞上均有表达。程序性细胞死亡 1（PD-1）/PD-L1 通路抑制宿主抗肿瘤反应，但对于 PD-1/PD-L1 在肿瘤微环境中的表达意义知之甚少。为了研究 PD-L1 表达在成人 T 细胞白血病/淋巴瘤（ATLL）中的临床病理影响，我们对 135 例 ATLL 活检样本进行了 PD-L1 免疫染色。我们观察到 2 个主要群体：1 个群体中淋巴瘤细胞有明显的 PD-L1 表达（nPD-L1(+)，占患者的 7.4%），另一个群体中淋巴瘤细胞表达最小（nPD-L1(-)，占 92.6%）。在 nPD-L1(-)组内，出现了 2 个亚群：第 1 个亚群中肿瘤微环境中非恶性基质细胞中大量表达 PD-L1（miPD-L1(+)，占 58.5%），第 2 个亚群中任何细胞均不表达 PD-L1（PD-L1(-)，占 34.1%）。nPD-L1(+) ATLL（中位总生存期[MST]为 7.5 个月，95%CI [0.4-22.3]）的总体生存（OS）较 nPD-L1(-) ATLL（MST 为 14.5 个月，95%CI [10.1-20.0]）差（P=.0085）。在 nPD-L1(-) ATLL 中，miPD-L1(+) ATLL（MST 为 18.6 个月，95%CI [11.0-38.5]）的 OS 优于 PD-L1(-) ATLL（MST 为 10.2 个月，95%CI [8.0-14.7]）（P=.0029）。多变量分析显示，nPD-L1 和 miPD-L1 的表达对 OS 有预后价值（P=.0322 和 P=.0014）。这是首个描述 ATLL 中 PD-L1 表达的临床病理特征和结局的报告。更详细的研究将揭示 PD-L1 表达在 ATLL 中的临床和生物学意义。
