Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Int Immunopharmacol. 2021 Apr;93:107371. doi: 10.1016/j.intimp.2021.107371. Epub 2021 Jan 31.
To explore the molecular mechanism in the esophageal squamous carcinoma (ESCC) environment, we selected datasets of ESCC patients from The Cancer Genome Atlas (TCGA) (n = 78) and explored the infiltration condition of 24 immune cells in each sample. We assorted the microenvironment of ESCC into two Infiltration groups (I and II) and built a random forest classifier model. We showed traits of gene and clinicopathology in the tumor microenvironment (TME) phenotypes systematically. Infiltration I had low infiltration of immune cells and immunomodulators but relatively higher mutation load, while Infiltration II was enriched with cytotoxic T cells and immunosuppressive cells. The upregulation of several immune cytokines like IFN-γ, TNF-β, and PD-L1 was seen in Infiltration II. The infiltration group was an independent predictor of prognosis showed by Multivariable Cox analysis (Infiltration II vs. I, hazard ratio = 2.73, 95% confidence interval = 1.08-6.91, p = 0.03). All the results can be verified in datasets from the Gene Expression Omnibus database (GEO) and our institution (n = 98). Our results demonstrate a synthesis of the infiltration pattern of the immune in ESCC. We reveal the mechanism of TME, which may contribute to the progress of immunotherapy for patients with ESCC.
为了探索食管鳞癌（ESCC）环境中的分子机制，我们从癌症基因组图谱（TCGA）中选择了 ESCC 患者的数据集（n=78），并探索了每个样本中 24 种免疫细胞的浸润情况。我们将 ESCC 的微环境分为两个浸润组（I 和 II），并构建了随机森林分类器模型。我们系统地展示了肿瘤微环境（TME）表型中的基因和临床病理特征。浸润 I 组免疫细胞和免疫调节剂浸润程度较低，但突变负荷相对较高，而浸润 II 组富含细胞毒性 T 细胞和免疫抑制细胞。在浸润 II 组中，几种免疫细胞因子如 IFN-γ、TNF-β 和 PD-L1 的表达上调。多变量 Cox 分析显示，浸润组是预后的独立预测因子（浸润 II 与 I 相比，危险比=2.73，95%置信区间=1.08-6.91，p=0.03）。所有结果都可以在 GEO 和我们机构的数据集（n=98）中得到验证。我们的研究结果综合了 ESCC 中免疫浸润的模式。我们揭示了 TME 的机制，这可能有助于为 ESCC 患者的免疫治疗进展做出贡献。
