Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing, China.
J Leukoc Biol. 2022 Oct;112(4):931-938. doi: 10.1002/JLB.5MA0422-505R. Epub 2022 Jun 3.
According to the Correa model, the intestinal-type gastric cancer (GC) is preceded by premalignant lesions, including chronic gastritis, intestinal metaplasia and dysplasia. However, the dynamic change of innate and adaptive immune response during this process has not been studied comprehensively. In this study, we performed a comprehensive and trajectory analysis of circulating innate lymphoid cells (ILCs) and adaptive Th lymphocytes subtypes in patients spanning a cascade of gastric lesions. Increased circulating ILC2s frequency was found in the gastritis, premalignant stage and GC group, whereas further decreased ILC2s were detected in the GC group compared with the premalignant group. Moreover, ILC3s level was higher in both gastritis, premalignant lesion and GC stage, compared with healthy controls. Furthermore, up-regulated T follicular helper (Tfh) cell proportions were detected in the gastritis and premalignant process. In conclusion, by analyzing the circulating ILCs and Th cells frequency and the key cytokine production or immunoglobulin level, we demonstrated the potential involvement of ILC3 and Tfh in the gastric diseases. These findings will help to understand the immunologic mechanisms in both GC and the premalignant process and contribute to serve potential therapeutic targets to prevent the GC development.
根据 Correa 模型，肠型胃癌（GC）之前存在癌前病变，包括慢性胃炎、肠上皮化生和异型增生。然而，在此过程中固有和适应性免疫反应的动态变化尚未得到全面研究。在这项研究中，我们对跨越胃病变级联的患者进行了循环固有淋巴细胞（ILC）和适应性 Th 淋巴细胞亚型的全面和轨迹分析。在胃炎、癌前病变和 GC 组中发现循环 ILC2 频率增加，而与癌前病变组相比，GC 组中进一步降低了 ILC2。此外，与健康对照组相比，在胃炎、癌前病变和 GC 阶段，ILC3 水平更高。此外，在胃炎和癌前病变过程中检测到滤泡辅助性 T（Tfh）细胞比例上调。总之，通过分析循环 ILC 和 Th 细胞频率以及关键细胞因子产生或免疫球蛋白水平，我们证明了 ILC3 和 Tfh 在胃疾病中的潜在作用。这些发现将有助于了解 GC 和癌前病变过程中的免疫机制，并有助于确定预防 GC 发展的潜在治疗靶点。
