Zhang Hong, Yue Rongxi, Zhao Pengfei, Yu Xuetao, Li Junguo, Ma Guoqing, Tang Jiahong, Zhang Lixin, Feng Liying, Sun Lidong, Song Zongchang, Guo Chunliang, Wang Ning
1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China.
2 Department of Oncology, Tianyou Hospital, Tongji University, Shanghai, China.
Tumour Biol. 2017 Jun;39(6):1010428317705747. doi: 10.1177/1010428317705747.
Gastric cancer is one of the most common and aggressive malignancies. Both bacterial virulence factors and host chronic inflammation are thought to promote gastric cancer development. In this study, we investigated the potential involvement of follicular helper T cells in gastric cancer. Functions of follicular helper T subsets were examined in Helicobacter pylori-infected gastric cancer patients and H. pylori-infected but asymptomatic individuals. We found that the follicular helper T cells in gastric cancer individuals were skewed toward the Th1 and Th17 subsets compared to those in H. pylori-infected but asymptomatic individuals. In a naive B cell-follicular helper T cell coculture, the Th1-follicular helper T cells by themselves were ineffective at stimulating a robust antibody response, unlike the Th2-follicular helper T and Th17-follicular helper T cells. However, Th1-follicular helper T cells significantly promoted the immunoglobulin G response in collaboration with other follicular helper T subsets, through the secretion of interferon gamma. We also found that Th1-follicular helper T cells suppressed the development of interleukin-10 regulatory B cells, a cell type previously thought to protect H. pylori-infected individuals from tissue damage. In addition, the frequency of Th1-follicular helper T cells in gastric cancer patients was negatively correlated with the disease-free survival of gastric cancer patients after tumor resection. These results suggested that dysregulation of follicular helper T subsets in gastric cancer patients, characterized by increased Th1-follicular helper T cells, contributed to inflammation and tumor development.
胃癌是最常见且侵袭性最强的恶性肿瘤之一。细菌毒力因子和宿主慢性炎症均被认为可促进胃癌的发生发展。在本研究中，我们调查了滤泡辅助性T细胞在胃癌中的潜在作用。在幽门螺杆菌感染的胃癌患者以及幽门螺杆菌感染但无症状的个体中检测了滤泡辅助性T细胞亚群的功能。我们发现，与幽门螺杆菌感染但无症状的个体相比，胃癌个体中的滤泡辅助性T细胞倾向于Th1和Th17亚群。在初始B细胞 - 滤泡辅助性T细胞共培养中，与Th2 - 滤泡辅助性T细胞和Th17 - 滤泡辅助性T细胞不同，Th1 - 滤泡辅助性T细胞自身在刺激强烈抗体反应方面无效。然而，Th1 - 滤泡辅助性T细胞通过分泌干扰素γ与其他滤泡辅助性T细胞亚群协同作用，显著促进了免疫球蛋白G反应。我们还发现，Th1 - 滤泡辅助性T细胞抑制了白细胞介素10调节性B细胞的发育，这种细胞类型此前被认为可保护幽门螺杆菌感染个体免受组织损伤。此外，胃癌患者中Th1 - 滤泡辅助性T细胞的频率与肿瘤切除后胃癌患者的无病生存期呈负相关。这些结果表明，以Th1 - 滤泡辅助性T细胞增加为特征的胃癌患者滤泡辅助性T细胞亚群失调促成了炎症和肿瘤发展。
