Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Jpn J Clin Oncol. 2021 Jul 1;51(7):1067-1079. doi: 10.1093/jjco/hyab054.
The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor-infiltrating immune cells activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer immune cell infiltration has not been identified so far.
In this study, we comprehensively analyzed the tumor-infiltrating immune cells abundance in gastric cancer for the first time by CIBERSORT. The meta-analysis, single-sample gene set enrichment analysis and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. The fraction of tumor-infiltrating immune cells subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes.
Tumor-infiltrating immune cells are extensively involved in the pathogenesis and development of the gastric cancer. We discovered Tfh and activated CD4+ memory T cells were associated with poorer overall survival and Progression-free survival (PFS), but that naïve B cells were opposite for PFS. Unsupervised clustering analysis revealed there existed three tumor-infiltrating immune cells subgroups with distinct survival patterns. Specially, cluster 1 showed significantly better clinical outcome than other two clusters.
Collectively, our data explored the differences of tumor-infiltrating immune cells in gastric cancer, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.
癌症的恶性表型不仅由其内在的肿瘤细胞定义，还由浸润肿瘤的免疫细胞所决定，这些细胞被募集到肿瘤微环境中。然而，目前尚未全面确定胃癌免疫细胞浸润的情况。
本研究首次通过 CIBERSORT 对胃癌中的肿瘤浸润免疫细胞丰度进行了全面分析。使用归一化基因表达数据，通过荟萃分析、单样本基因集富集分析和层次聚类分析，测量和评估了 22 种免疫浸润细胞类型各自的比例。还评估了肿瘤浸润免疫细胞亚群的比例，以确定与临床特征和分子亚型的关联。
肿瘤浸润免疫细胞广泛参与胃癌的发病机制和发展。我们发现滤泡辅助性 T 细胞（Tfh）和激活的 CD4+记忆 T 细胞与总生存期（OS）和无进展生存期（PFS）较差相关，而幼稚 B 细胞与 PFS 相反。非监督聚类分析显示存在三个具有不同生存模式的肿瘤浸润免疫细胞亚群。特别是，簇 1 的临床结局明显优于其他两个簇。
总之，我们的数据探讨了胃癌中肿瘤浸润免疫细胞的差异，这些变化可能是其未来临床应用预后和管理的重要线索。
