Preferential Tim-3 expression on Treg and CD8(+) T cells, supported by tumor-associated macrophages, is associated with worse prognosis in gastric cancer.
Year: 2016
Type: article
Study design: Observational Study
Abstract: While infection with H. pylori is a strong risk factor for gastric cancer, most H. pylori-colonized individuals, even those with the high-risk CagA(+)VacA(+) strain, remain asymptomatic over their lifetime. We hypothesized that the discordant outcomes were due to differences in the host immune responses. Previously, Tim-3-mediated immune modulation was observed in H. pylori-challenged mice. In this study, we compared Tim-3-related responses in CagA(+)VacA(+) H. pylori-infected asymptomatic individuals and H. pylori-associated gastric adenocarcinoma patients. We showed that compared to H. pylori-uninfected individuals, both H. pylori-infected asymptomatic and gastric cancer patients upregulated Tim-3 overall. However, the Tim-3 upregulation was enriched on Th1 cells in asymptomatic patients and on Treg and CD8(+) T cells in gastric cancer patients, with respective differences in T cell subset functions. In gastric cancer patients, high Tim-3 expression on Treg and CD8(+) T cells, but not on Th1 cells, was associated with worse prognosis. H. pylori-antigen presentation by tumor-associated macrophages upregulated Tim-3 expression more effectively than by blood monocyte-derived macrophages in vitro. The upregulation of Tim-3 in vitro depended on the concentration of H. pylori antigen but not on whether the cells were from asymptomatic or cancer patients. These data suggest that the discrepancy in Tim-3 upregulation in asymptomatic and cancer subjects is induced by cancer but not the other way around. Once gastric cancer is developed, Tim-3 expression is associated with worse prognosis.
Source: Europe PMC (PubMed Central)
Authors: Pinying Shen, Rongxi Yue, Jiahong Tang, Haige Si, Liqun Shen, Changsheng Guo, Lixin Zhang, Huaizhong Han, Haihan K Song, Pengfei Zhao, Ning Wang, Zongchang Song, Chunliang Guo
Institution: Kaifeng University
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2533728704