Ahn Hyein, Yang Jeong Mi, Kim Hyojin, Chung Jin-Haeng, Ahn Soon-Hyun, Jeong Woo-Jin, Paik Jin Ho
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Oncotarget. 2017 Aug 3;8(39):66178-66194. doi: 10.18632/oncotarget.19842. eCollection 2017 Sep 12.
Immune escape of a tumor from tumor-infiltrating lymphocytes (TILs) is induced by PD-L1, which is suppressed by miR-197. We investigated the clinicopathologic implications of the miR-197/PD-L1 axis and its effects on TILs and the clinicopathologic features of oral squamous cell carcinoma (OSCC). We used RT-PCR and immunohistochemistry in 68 OSCC patients to analyze the correlations between tumoral expression of miR-197 and PD-L1 and the degree of tumoral invasion by TILs (CD3+, CD4+, CD8+, PD-1+, FoxP3+, and CD20+ lymphocytes). PD-L1 levels correlated inversely with miR-197 but correlated positively with TILs. The aggressive features of OSCC, including high stage, angiolymphatic invasion, perineural invasion, and death, were associated with TIL depletion. High T stage (T4) tumors also had low PD-L1 but had high miR-197 expression. In a univariate survival analysis of the full cohort, high miR-197 was associated with poor overall survival, whereas high PD-L1 expression (2+) associated with good overall survival. In a multivariate analysis stratified based on miR-197 (median), high PD-L1 expression (2+) was an independent favorable prognostic factor for overall survival ( = 0.040) in the miR-197 subgroup but not the miR-197 subgroup. These findings may have clinicopathologic implications for the miR-197/PD-L1 axis and TILs in OSCC.
肿瘤的免疫逃逸是由程序性死亡配体1(PD-L1)诱导产生的,而微小RNA-197(miR-197)可抑制PD-L1。我们研究了miR-197/PD-L1轴的临床病理意义及其对肿瘤浸润淋巴细胞(TILs)的影响,以及其对口腔鳞状细胞癌(OSCC)临床病理特征的影响。我们对68例OSCC患者进行了逆转录聚合酶链反应(RT-PCR)和免疫组织化学检测,以分析miR-197和PD-L1的肿瘤表达与TILs(CD3 +、CD4 +、CD8 +、PD-1 +、FoxP3 +和CD20 +淋巴细胞)的肿瘤浸润程度之间的相关性。PD-L1水平与miR-197呈负相关,但与TILs呈正相关。OSCC的侵袭性特征,包括高分期、血管淋巴管浸润、神经周围浸润和死亡,都与TILs减少有关。高T分期(T4)肿瘤的PD-L1水平也较低,但miR-197表达较高。在整个队列的单因素生存分析中,高miR-197与总生存期较差相关,而高PD-L1表达(2+)与总生存期良好相关。在基于miR-197(中位数)分层的多因素分析中,高PD-L1表达(2+)是miR-197亚组总生存期的独立有利预后因素(P = 0.040),但在miR-197亚组中并非如此。这些发现可能对OSCC中miR-197/PD-L1轴和TILs具有临床病理意义。