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Clinicopathological features of programmed cell death-1 and programmed cell death-ligand-1 expression in the tumor cells and tumor microenvironment of angioimmunoblastic T cell lymphoma and peripheral T cell lymphoma not otherwise specified.
Virchows Archiv ( IF 3.5 ) Pub Date : 2020-03-13 , DOI: 10.1007/s00428-020-02790-z
Sehui Kim 1, 2 , Dohee Kwon 1 , Jiwon Koh 1 , Soo Jeong Nam 3 , Young A Kim 4 , Tae Min Kim 5 , Chul Woo Kim 1, 2 , Yoon Kyung Jeon 1, 2
Affiliation  

The expression patterns of programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) and their clinicopathological implications were investigated in peripheral T cell lymphoma (PTCL) including angioimmunoblastic T cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS). PTCL-NOS was further classified into nodal PTCL with follicular helper T cell (Tfh) phenotype (“PTCL-Tfh_new”) and “PTCL-NOS_new”. PD-1 and PD-L1 expression on tumor cells and reactive immune cells was evaluated using immunohistochemistry. PD-1 and PD-L1 expression on tumor cells (PD-1T and PD-L1T, respectively) was interpreted as positive when more than 5% of tumor cells expressed PD-1 or PD-L1. For PD-1 and PD-L1 on tumor cells and/or reactive immune cells (PD-1T + IC and PD-L1T + IC, respectively), a cutoff of 10% of cells was used. PD-1T, PD-L1T, and PD-L1T + IC expressions tended to be higher in AITLs than in PTCLs-NOS. PD-1T, PD-1T + IC, PD-L1T, and PD-L1T + IC expressions tended to be higher in PTCLs with Tfh phenotype including AITLs and “PTCL-Tfh_new” than in PTCLs without Tfh phenotype. The serum LDH level was significantly elevated in patients with PTCL positive for PD-L1T (P = 0.006) and PD-L1T + IC (P < 0.001). Patients with PTCL who were positive for combined expression of PD-1T/PD-L1T + IC presented at older ages (P = 0.010), nodal diseases (P = 0.001), higher IPI (P = 0.060), and elevated LDH (P = 0.030). Combined PD-1T/PD-L1T + IC positivity was related to shorter overall survival in patients with AITL (P = 0.051). Combined PD-1T/PD-L1T + IC positivity was a significant poor prognostic factor in patients with stage IV AITL, independent of B symptoms and performance status (HR = 6.282 [CI, 1.655–23.844], P = 0.007). In summary, the PD-1/PD-L1 pathway could be a potential prognostic and therapeutic biomarker for PTCL.



中文翻译:

肿瘤细胞和血管免疫母细胞性T细胞淋巴瘤和外周T细胞淋巴瘤的肿瘤细胞和肿瘤微环境中程序性细胞死亡1和程序性细胞死亡配体-1表达的临床病理特征。

研究了程序性细胞死亡1(PD-1)和程序性细胞死亡配体-1(PD-L1)的表达模式及其在周围T细胞淋巴瘤(PTCL)中的临床病理意义,包括血管免疫母细胞性T细胞淋巴瘤(AITL)和PTCL-除非另有说明(PTCL-NOS)。PTCL-NOS进一步分为具有滤泡辅助性T细胞(Tfh)表型(“ PTCL-Tfh_new”)和“ PTCL-NOS_new”的结节PTCL。使用免疫组织化学评估肿瘤细胞和反应性免疫细胞上PD-1和PD-L1的表达。当超过5%的肿瘤细胞表达PD-1或PD-L1时,肿瘤细胞上的PD-1和PD-L1表达(分别为PD-1 T和PD-L1 T)被解释为阳性。对于肿瘤细胞和/或反应性免疫细胞上的PD-1和PD-L1(PD-1 T + IC和PD-L1 T + IC)分别使用10%的细胞截止值。AITL中的PD-1 T,PD-L1 T和PD-L1 T + IC表达倾向于高于PTCLs-NOS。具有Tfh表型(包括AITL)和“ PTCL-Tfh_new”的PTCL中的PD-1 T,PD-1 T + IC,PD-L1 T和PD-L1 T + IC的表达倾向于比没有Tfh表型的PTCL高。血清LDH水平的患者PTCL阳性PD-L1被显著升高ŤP  = 0.006)和PD-L1 T + ICP  <0.001)。PDL联合表达阳性的PTCL患者T / PD-L1 T + IC出现在较高年龄(P  = 0.010),淋巴结疾病(P  = 0.001),更高的IPI(P  = 0.060)和LDH升高(P  = 0.030)。PD-1 T / PD-L1 T + IC联合阳性与AITL患者总体生存期缩短有关(P  = 0.051)。合并PD-1 T / PD-L1 T + IC阳性是IV期AITL患者的显着不良预后因素,与B症状和表现状态无关(HR = 6.282 [CI,1.655–23.844],P = 0.007)。总之,PD-1 / PD-L1途径可能是PTCL的潜在预后和治疗生物标志物。

更新日期:2020-03-13
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