title: Upregulation of T-cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Monocytes/Macrophages Associates with Gastric Cancer Progression.
abstract: T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is an important immune regulatory molecule in cancer immune system. However, expression and function of Tim-3 in monocytes/macrophages in cancer progression mainly remain unclear. In this study, we analyzed Tim-3 levels in peripheral blood mononuclear cells (PBMCs) from 62 gastric cancer patients and 45 healthy controls using flow cytometry and then associated Tim-3 levels with clinical pathological data from patients. We found Tim-3 level was significantly upregulated in monocytes from gastric cancer patients compared with those from healthy controls, and that upregulated Tim-3 levels associated with depth of tumor invasion and tumor lymph node metastasis and advanced clinical stages of gastric cancer patients. Furthermore, tumor-bearing mouse experiments revealed that Tim-3 level on monocytes/macrophages associated with xenograft formation and growth. In addition, culture of monocytes from healthy controls with gastric cancer cell-conditioned medium upregulated Tim-3 expression, but IL-10, TNF-α, IFN-γ, or GM-CSF treatment or T-bet, Eomes, and T-bet/Eomes double gene knockout did not affect Tim-3 levels in blood monocytes/macrophages from human or mouse, respectively. Gal-9/Tim-3 signal was able to significantly stimulate monocyte to secrete IL-6, IL-8, and IL-10, but not IL-1β, IL-12p70, or TNF-α in presence of LPS. In conclusion, our study demonstrated that Tim-3 expressed by monocyte/macrophages might be an important mechanism in gastric cancer progression.
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Soochow University , Suzhou , China.|b Department of Medical Oncology , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: b Department of Medical Oncology , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Ni
authors.initials: N
authors.lastname: Yin
authors.affiliation: c Department of General Surgery , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: c Department of General Surgery , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: d Clinical Immunology of Jiangsu Province , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Soochow University , Suzhou , China.|d Clinical Immunology of Jiangsu Province , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D037161:Galectins / Q000378:metabolism*; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; C491198:Eomes protein, mouse; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C508186:galectin 9, mouse
keywords: Gastric cancer; Tim-3; monocyte/macrophage; tumor progression