Liu Yang, Ma Jing, Yu Kangjie, Li Mingyang, Liu Fang, Yan Qingguo, Wang Zhe, Guo Shuangping
State Key Laboratory of Tumor Biology, Department of Pathology, The Basic Medicine Science and Xi Jing Hospital, The Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Student Team 1, Class 3, The Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Pathol Res Pract. 2018 Apr;214(4):507-512. doi: 10.1016/j.prp.2018.03.001. Epub 2018 Mar 12.
Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma. However, there has not been a comprehensive investigation into the expression patterns of programmed cell death 1 (PD-1) and programmed cell death ligand 1(PD-L1) in GI DLBCL tissues.
PD-1 protein expression in tumor-infiltrating lymphocytes (TILs) was evaluated by immunohistochemical staining, and expression of PD-L1 was evaluated by using PD-L1/PAX5 immunohistochemical double staining in 92 GI DLBCL specimens.
The prevalence of positive PD-L1 expression (PD-L1 + ) in GI DLBCL cells and positive PD-L1 expression in non-cancer cells of the GI DLBCL microenvironment (microenvironmental PD-L1, mPD-L1) were 11.96% (11 of 92) and 41.98% (34 of 81), respectively. PD-L1 expression in GI DLBCL was significantly associated with involvement of extranodal sites ≥ 2 (P = 0.034) and mPD-L1 expression was significantly associated with ECOG performance status (score ≥ 2) (P = 0.041). PD-L1 expression and mPD-L1 expression had no prognostic significance (P > 0.05) on disease outcome. PD-1+ TILs were significantly lower in patients with extranodal site involvement (P = 0.011) and the quantity of PD-1 + TILs correlated positively with the level of PDL1 expression in non malignant microenvironment cells (P = 0.001). Patients with high levels of PD-1+ TILs had better prognosis (P = 0.0005).
The expression patterns of PD-L1 in patients with GI DLBCL are different from patients with common DLBCL. Immunotherapies that target the PD-1/PD-L1 pathway may have therapeutic potential in GI DLBCL.
胃肠道弥漫性大B细胞淋巴瘤(GI DLBCL)是最常见的胃肠道淋巴瘤。然而,尚未对GI DLBCL组织中程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡配体1(PD-L1)的表达模式进行全面研究。
通过免疫组织化学染色评估肿瘤浸润淋巴细胞(TILs)中PD-1蛋白的表达,并使用PD-L1/PAX5免疫组织化学双重染色评估92例GI DLBCL标本中PD-L1的表达。
GI DLBCL细胞中PD-L1阳性表达(PD-L1+)的发生率和GI DLBCL微环境中非癌细胞中PD-L1阳性表达(微环境PD-L1,mPD-L1)的发生率分别为11.96%(92例中的11例)和41.98%(81例中的34例)。GI DLBCL中PD-L1的表达与≥2个结外部位受累显著相关(P = 0.034),mPD-L1的表达与ECOG体能状态(评分≥2)显著相关(P = 0.041)。PD-L1表达和mPD-L1表达对疾病转归无预后意义(P>0.05)。结外部位受累患者的PD-1+ TILs显著降低(P = 0.011),PD-1+ TILs的数量与非恶性微环境细胞中PDL1表达水平呈正相关(P = 0.001)。PD-1+ TILs水平高的患者预后较好(P = 0.0005)。
GI DLBCL患者中PD-L1的表达模式与普通DLBCL患者不同。靶向PD-1/PD-L1途径的免疫疗法可能对GI DLBCL具有治疗潜力。