title: Preferential Tim-3 expression on Treg and CD8(+) T cells, supported by tumor-associated macrophages, is associated with worse prognosis in gastric cancer.
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.
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Pinying
authors.initials: P
authors.lastname: Shen
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Rongxi
authors.initials: R
authors.lastname: Yue
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Tang
authors.affiliation: College of Foreign Languages, Kaifeng University Kaifeng City, Henan Province 475000, China.
authors.forename: Haige
authors.initials: H
authors.lastname: Si
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Shen
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Guo
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Huaizhong
authors.initials: H
authors.lastname: Han
authors.affiliation: DICAT Biomedical Computation Centre British Columbia, Canada.
authors.forename: Haihan K
authors.initials: HK
authors.lastname: Song
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhao
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Zongchang
authors.initials: Z
authors.lastname: Song
authors.affiliation: The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City Kaifeng City, Henan Province 475003, China.
authors.forename: Chunliang
authors.initials: C
authors.lastname: Guo
keywords: H. pylori; Tim-3; gastric cancer