The Clinical and Biological Effects of PD-1 Expression on Tumor Cells in Diffuse Large B-Cell Lymphoma
The Clinical and Biological Effects of PD-1 Expression on Tumor Cells in Diffuse Large B-Cell Lymphoma
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DOI：
10.3390/hemato2020023
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发表时间：
2021-06-01
期刊：
影响因子：
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通讯作者：
Takami, Akiyoshi
中科院分区：
文献类型：
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作者：
Hanamura, Ichiro;Suzuki, Susumu;Takami, Akiyoshi
程序性死亡-1 （PD-1）在b淋巴瘤细胞表达的临床和生物学意义在很大程度上是未知的。在这里，我们使用多色免疫荧光染色（MC-IF），研究了PD-1和PD-L1在福尔马林固定、石蜡包埋的32例连续接受利妥昔单抗加化疗的新生弥漫性大b细胞淋巴瘤（DLBCL）患者的PAX5+ （b淋巴瘤）、CD68+（巨噬细胞）或CD3+ （t细胞）细胞中的表达。在59%和3%的患者中分别观察到表达PD-1和pd - l1的PAX5+细胞。pd -1表达CD3+淋巴细胞和pd - l1表达CD68+巨噬细胞分别占89%和86%。PAX5+淋巴瘤细胞或CD68+巨噬细胞上PD-L1表达和CD3+淋巴细胞上PD-1表达与预后无相关性。然而，淋巴瘤细胞上PD-1表达的患者的无进展生存期比缺乏PD-1表达的淋巴瘤细胞的患者短（p = 0.033）。此外，与VAL/模拟细胞相比，基因修饰pd -1敲除的人b淋巴瘤VAL细胞表现出细胞生长和迁移减少，S6激酶磷酸化降低。我们的数据表明，MC-IF检测到的DLBCL细胞上的PD-1表达与不良预后有关，细胞内PD-1信号传导与b细胞淋巴瘤亚群中的细胞生长和迁移有关。这些发现可能允许发展不同的影响预后的DLBCL亚型。
The clinical and biological significance of programmed death-1 (PD-1) expression by B-lymphoma cells is largely unknown. Here, using multicolor immunofluorescent staining (MC-IF), we investigated PD-1 and PD-L1 expression in PAX5+ (B-lymphoma), CD68+ (macrophage), or CD3+ (T-cell) cells in formalin-fixed, paraffin-embedded samples of 32 consecutive patients with de novo diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus chemotherapy. PD-1- and PD-L1-expressing PAX5+ cells were observed in 59% and 3% of the patients, respectively. PD-1-expressing CD3+ lymphocytes and PD-L1-expressing CD68+ macrophages were observed in 89% and 86% of the patients, respectively. PD-L1 expression on PAX5+ lymphoma cells or CD68+ macrophages and PD-1 expression on CD3+ lymphocytes were not correlated with prognosis. However, patients with PD-1 expression on lymphoma cells showed shorter progression-free survival than those lacking PD-1-expressing lymphoma cells (p = 0.033). Furthermore, genetically modified PD-1-knockout human B-lymphoma VAL cells showed reduced cell growth and migration, and decreased S6 kinase phosphorylation than VAL/mock cells. Our data suggest that PD-1 expression on DLBCL cells detected by MC-IF was associated with poor prognosis and cell-intrinsic PD-1 signaling was related with cell growth and migration in a subpopulation of B-cell lymphoma. These findings may allow the development of distinct DLBCL subtypes affecting prognosis.