Department of Pathology, University Medical Center Utrecht, The Netherlands.
Department of Pathology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Oral Oncol. 2017 Aug;71:16-25. doi: 10.1016/j.oraloncology.2017.05.015. Epub 2017 Jun 3.
Tumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC.
Tissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant.
EBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075-0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010-0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195-0.850)) and OS (HR 0.170 (95%CI 0.037-0.787)).
Although TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment.
肿瘤浸润淋巴细胞（TILs）与实体瘤的预后较好和较差相关。由于鼻咽癌（NPC）的治疗方法有限，免疫疗法可能是一种潜在的选择。到目前为止，关于 TILs 在 NPC 中的作用的预后数据有限，因此我们评估了 TILs 在 EBV 阳性和阴性 NPC 中的预后作用。
评估了 92 例 NPC 组织中肿瘤微环境中 CD3、CD4、CD8、PD1 和 PDL1 的表达。使用 Pearson X 检验、Fisher 精确检验和 ANOVA 评估临床病理特征之间的相关性。使用 Kaplan-Meier 方法和 Cox 回归分析生存情况。使用 Mann-Whitney U 检验评估 EBV 阳性和阴性 NPC 之间 CD3、CD4、CD8、PD1、PDL1 计数/（共）表达的差异。双侧 P 值<0.05 被认为具有统计学意义。
EBV 阳性 NPC 中 CD3、CD4 和 CD8 TILs 的含量明显高于 EBV 阴性 NPC。在整个 NPC 组中，CD8 计数的增加与总生存期（OS）的改善相关（HR 0.219（95%CI 0.075-0.640）），但在 PDL1 共表达的情况下也是如此（HR 0.073（95%CI 0.010-0.556））。在 EBV 阳性 NPC 中，CD8 和 PDL1 的共表达显示出更好的无病生存期（HR 0.407（95%CI 0.195-0.850））和 OS（HR 0.170（95%CI 0.037-0.787））。
尽管 EBV 阳性和阴性 NPC 之间的 TILs 存在显著差异，但浸润的组成决定了预后。PD1 和 CD8 的作用还需要更多的研究，因为这些发现显示出在 NPC 治疗中使用免疫治疗方法的巨大潜力。
