Comment on “Genomic Alteration and Immunity: Implications in Esophageal Cancer”
Comment on “Genomic Alteration and Immunity: Implications in Esophageal Cancer”
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对“基因组改变和免疫：对食管癌的影响”的评论
DOI：
10.1097/sla.0000000000004952
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发表时间：
2021
影响因子：
9
通讯作者：
Xiaofei Shen
中科院分区：
文献类型：
--
作者：
Junfeng Du;Xiaofei Shen
致编辑：我们饶有兴趣地阅读了Kosumi等人1的文章，该文章显示了食管癌中肿瘤长散布核苷酸元件-1（LINE-1）甲基化水平与免疫反应之间的关系。我们对目前的研究结果和同一小组在《外科年鉴》上发表的其他几项研究结果印象深刻。在我们看来，几乎相同的研究人群在本研究中使用，与以往的研究阐明免疫反应在预测食管癌预后的作用。2，3结合这些结果，作者为我们提供了关于肿瘤发生中表观遗传调控和宿主免疫的深入思考。但是，我们仍然要提出以下关切。首先，目前的研究表明肿瘤LINE-1水平对食管癌患者的预后具有预测作用，并且仅与肿瘤周围淋巴细胞反应（PLR）减弱相关，而与其他潜在的免疫参数如T细胞密度、程序性死亡配体1和吲哚胺2，3-双加氧酶1水平无关。同一研究小组先前的研究表明，通过使用相同的研究人群，这些免疫参数在食管癌预后中起着关键作用。2，3因此，表观遗传学改变和免疫应答在预测食管癌的预后中发挥作用，这可能是肿瘤发生和发展的两个主要因素。这引起了一个可能的问题，即哪个参数在预测食管癌的预后和指导后续治疗中最重要，尽管有共同的病理特征。在分析食管癌患者的预后时，这些参数是否会相互影响？通过基于同一研究人群的多变量分析来解决这些问题将是非常重要的，因为评估人群中肿瘤特征和肿瘤免疫的目的是提供更基本的无偏信息，以更好地了解临床和预后特征。第二，LINE-1甲基化水平在不同阶段的患者中是不同的，在晚期患者中存在低甲基化水平。基于当前研究的结论，LINE-1的低甲基化水平与低得多的PLR水平相关，这表明免疫应答受损。然而，这与同一组先前产生的结果相反，2该结果显示肿瘤浸润淋巴细胞阳性（定义为肿瘤浸润边缘的淋巴细胞浸润）与晚期显著相关。这提出了一个重要的问题，即PLR和肿瘤浸润淋巴细胞是否实际上代表了完全不同的免疫反应，或者当前和以前的研究之间的差异仅仅是一个群体偏倚。因此，可能需要对不同阶段的患者进行肿瘤LINE-1低甲基化与PLR水平之间关系的亚组分析，以更好地了解低甲基化对肿瘤免疫的影响。与此类似，LINE-1低甲基化对预后的影响在I期食管癌中更为突出。4第三，虽然肿瘤LINE-1甲基化水平与外周血淋巴细胞之间的相关性显示出显著性，但相关曲线相对平坦，表明潜在的低相关程度。肿瘤LINE-1与PLR仅相关，但与PLR仍有显著相关性。
To the Editor: We read with interest the article by Kosumi et al1 which showed the relationship between tumor long-interspersed nucleotide element-1 (LINE-1) methylation level and immune response in esophageal cancer. We are impressed by the results from current study and several other studies published by the same group in Annals of Surgery. It seems to us that almost the same research population was used in the current study, compared with previous studies on elucidating the role of immune response in predicting the prognosis of esophageal cancer. 2, 3 Combing these results together, the authors provided us an in-depth thinking about epigenetic regulation and host immunity in tumor development. However, we still would like to raise the following concerns. First, current study suggested that tumor LINE-1 level had a prediction role in the outcome of patients with esophageal cancer, and was only associated with a diminished peritumoral lymphocytic reaction (PLR) but not with other potential immune parameters such as the density of T cells, programmed death-ligand 1, and indoleamine 2, 3-dioxygenase 1 levels. Previous studies by the same group have indicated the critical roles of these immune parameters in the prognosis of esophageal cancer through the use of the same research population. 2, 3 Therefore, both epigenetic changes and immune response were discovered to play roles in predicting the prognosis of esophageal cancer, which may act as two major factors in tumor development and progression. This raises a possible concern that which parameter is the most important in predicting the prognosis of esophageal cancer and guiding the following treatment, despite common pathological characteristics. Will these parameters influence each other when analyzing the outcome of patients with esophageal cancer? It would be of great importance to address these questions through the use of multivariable analyses based on the same research population, as the purpose of assessing tumor characteristics and tumor immunity in human population is to give more fundamental unbiased information to better understand the clinical and prognostic features.Second, the levels of LINE-1 methylation were different in patients with different stages, with a hypomethylation level in patients with advanced stages. Based on the conclusion from current study, a hypomethylation level of LINE-1 was associated with a much lower level of PLR, which indicated a compromised immune response. However, this was in contrary to the results generated by the same group previously, 2 which showed that tumor-infiltrating lymphocytes positivity (defined as lymphocytes infiltration in the tumor invasive margin) was significantly associated with advanced stages. This raises an important question that whether PLR and tumor-infiltrating lymphocytes may actually represent totally different immune responses or the difference between current and previous studies is simply a population bias. Therefore, subgroups analyses of patients at different stages on the relationship between tumor LINE-1 hypomethylation and PLR level may be required to better understand the effect of hypomethylation on tumor immunity. Similar with these, the effect of LINE-1 hypomethylation on the prognosis was more prominent among stage I esophageal cancer. 4 Third, although the association between tumor LINE-1 methylation level and peripheral blood lymphocytes showed significance, the correlation curve was relatively flat, indicating a potential low degree of correlation. It was also interesting that tumor LINE-1 was only relative to PLR but still showed significant relationship with …