DataSheet_1_Immune Profiling in Gastric Cancer Reveals the Dynamic Landscape of Immune Signature Underlying Tumor Progression.pdf

The profiling of the tumor immune microenvironment (TIME) is critical for guiding immunotherapy strategies. However, how the composition of the immune landscape affects the tumor progression of gastric cancer (GC) is ill-defined. Here, we used mass cytometry to perform simultaneous in-depth immune profiling of the tumor, adjacent tissues, and blood cells from GC patients and revealed a unique GC tumor-immune signature, where CD8+ T cells were present at a lower frequency in tumor tissues compared to adjacent tissues, whereas regulatory T cells and tumor-associated macrophages (TAMs) were significantly increased, indicating strong suppressive TIME in GC. Incorporated with oncogenic genomic traits, we found that the unique immunophenotype was interactively shaped by a specific GC gene signature across tumor progression. Earlier-stage GC lesions with IFN signaling enrichment harbored significantly altered T-cell compartments while advanced GC featured by metabolism signaling activation was accumulated by TAMs. Interestingly, PD-1 expression on CD8+ T cells was relatively higher in earlier-stage GC patients, indicating that these patients may derive more benefits from PD-1 inhibitors. The dynamic properties of diverse immune cell types revealed by our study provide new dimensions to the immune landscape of GC and facilitate the development of novel immunotherapy strategies for GC patients.

肿瘤免疫微环境（tumor immune microenvironment, TIME）的特征解析对于指导免疫治疗策略至关重要。然而，免疫景观的组成如何影响胃癌（gastric cancer, GC）的肿瘤进展，目前仍未明确。本研究采用质谱流式细胞术，对胃癌患者的肿瘤组织、癌旁组织及外周血细胞开展同步的深度免疫特征分析，揭示了独特的胃癌肿瘤免疫特征：相较于癌旁组织，肿瘤组织中CD8+ T细胞的占比更低，而调节性T细胞与肿瘤相关巨噬细胞（tumor-associated macrophages, TAMs）则显著升高，提示胃癌存在极强的免疫抑制性肿瘤免疫微环境。结合致癌基因组特征分析后，本研究发现，独特的免疫表型由跨肿瘤进展阶段的特异性胃癌基因特征交互塑造。干扰素信号通路富集的早期胃癌病灶呈现T细胞亚群显著改变，而以代谢信号通路激活为特征的进展期胃癌则出现肿瘤相关巨噬细胞的累积。有趣的是，早期胃癌患者CD8+ T细胞上的PD-1表达水平相对更高，提示此类患者或可从PD-1抑制剂治疗中获益更多。本研究揭示的多种免疫细胞类型的动态特性，为胃癌免疫景观提供了新的研究维度，也有助于推动胃癌患者新型免疫治疗策略的开发。