Programmed cell death-ligand 1 (PD-L1)+ tumour cells and low-reacting programmed cell death 1 (PD1)+ tumour-infiltrating lymphocytes predict poor prognosis in Epstein-Barr virus+ diffuse large B-cell lymphoma
Programmed cell death-ligand 1 (PD-L1)+ tumour cells and low-reacting programmed cell death 1 (PD1)+ tumour-infiltrating lymphocytes predict poor prognosis in Epstein-Barr virus+ diffuse large B-cell lymphoma
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DOI：
10.1007/s10238-021-00754-4
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发表时间：
2021-09-13
影响因子：
4.6
通讯作者：
Takeshita, Morishige
中科院分区：
文献类型：
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作者：
Kimura, Shoichi;Oshiro, Yumi;Takeshita, Morishige
eb病毒（EBV）（+）弥漫性大b细胞淋巴瘤（DLBCL）具有特定的肿瘤细胞特征，这些患者的预后比EBV阴性DLBCL患者更差。我们比较了38例EBV+ DLBCL患者的43例甲氨蝶呤相关EBV+ b细胞淋巴增生性疾病（MTX+/EBV+ blpd）和30例非生发中心（GC）亚型DLBCL。EBV+ DLBCL组淋巴瘤细胞BCL2阳性17例（44.7%），CMYC阳性23例（60.5%），p53阳性33例（86.8%），显著高于MTX+/EBV+ BLPD组（P < 0.05）， CD30阳性29例（76.3%），而非gc亚型DLBCL阳性2例（6.7%）（P < 0.0001）。EBV+ DLBCL患者（n = 16, 42.1%）的程序性细胞死亡-配体1(PD-L1)（+）肿瘤细胞明显多于非gc亚型DLBCL患者（n = 5, 16.7%, P = 0.024）， PD-L1（+）肿瘤细胞在晚期比早期更常见（P = 0.048）。25例EBV+ DLBCL患者（69.4%）很少有反应性PD1（+）肿瘤浸润淋巴细胞（til），而12例MTX+/EBV+ blpd患者（37.5%）（P = 0.008）。在EBV+ DLBCL组中，CD30、BCL2、CMYC和p53的表达与患者预后无关。不良结果与PD-L1（+）肿瘤细胞（P = 0.001）和低反应的PD1(+) til （P = 0.02）相关，而它们的联合导致更差的结果（P < 0.0001）。EBV+ DLBCL患者可能发生PD-L1（+）肿瘤细胞的免疫逃避和PD1(+) til的耗尽，PD-L1/PD1相互作用可能影响肿瘤进展和不良预后。
Epstein-Barr virus (EBV)(+) diffuse large B-cell lymphoma (DLBCL) has specific tumour cell characteristics, and these patients have worse outcomes than EBV-negative DLBCL patients. We compared 38 EBV+ DLBCL patients with 43 methotrexate-associated EBV+ B-cell lymphoproliferative disorders (MTX+/EBV+ BLPDs) and 30 non-germinal centre (GC) subtype DLBCL. Lymphoma cells of the EBV+ DLBCL group were positive for BCL2 in 17 patients (44.7%), CMYC in 23 patients (60.5%), and p53 in 33 patients (86.8%), which was significantly higher than in the MTX+/EBV+ BLPD group (P < 0.05), and were positive for CD30 in 29 patients (76.3%), compared with two in non-GC subtype DLBCL (6.7%) (P < 0.0001). Significantly more EBV+ DLBCL patients (n = 16, 42.1%) had programmed cell death-ligand 1 (PD-L1)(+) tumour cells than patients with non-GC subtype DLBCL (n = 5, 16.7%; P = 0.024), and PD-L1(+) tumour cells were more common in advanced stages than in early stages (P = 0.048). Twenty-five EBV+ DLBCL patients (69.4%) had few reactive PD1(+) tumour-infiltrating lymphocytes (TILs), compared with 12 patients with MTX+/EBV+ BLPDs (37.5%) (P = 0.008). In the EBV+ DLBCL group, CD30, BCL2, CMYC, and p53 expression was not related to patient prognosis. Poor outcomes were associated with PD-L1(+) tumour cells (P = 0.001) and low-reacting PD1(+) TILs (P = 0.02), while their combination conferred a worse outcome (P < 0.0001). Immune evasion by PD-L1(+) tumour cells and exhaustion of PD1(+) TILs may occur in EBV+ DLBCL patients, and PD-L1/PD1 interactions may influence tumour progression and poor prognosis.