title: Increased B7-H1 and B7-H4 Expressions on Circulating Monocytes and Tumor-Associated Macrophages are Involved in Immune Evasion in Patients with Gastric Cancer.
abstract: Expression of the costimulatory molecule B7-H4, a member of the inhibitory B7 family, has been reported to be upregulated on tumor-associated macrophages, and this overexpression may be involved in immune evasion in cancer patients. The present study was designed to investigate B7-H4 expression on monocytes/macrophages and its relationship with immune evasion in gastric cancer patients. B7-H4 expression on circulating monocytes and tumor-associated macrophages was evaluated by multicolor flow cytometry. Carboxyfluorescein succinimidyl ester proliferation assays and quantitative interferon-gamma enzyme-linked immunosorbent assays were carried out to determine the inhibitory effect of B7-H4+ monocytes on CD4+ T cells. B7-H4 expression on circulating monocytes was upregulated and these B7-H4+ monocytes showed immunosuppressive properties. B7-H4 expression was closely related to the depth of invasion, as well as the presence of lymphatic and venous invasion. There were significant correlations between B7-H4 expression and B7-H1 or HLA-DR expression on monocytes/macrophages in gastric cancer patients. B7-H4 expression was remarkably upregulated in gastric cancer tissues compared with peripheral blood samples. Complete surgical removal of the tumor decreased B7-H4 expression on circulating monocytes from gastric cancer patients. Cocultures of gastric cancer cell lines and monocytes led to upregulation of B7-H4 expression on monocytes. Increased B7-H4 expression on circulating monocytes and tumor-associated macrophages may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.forename: Masahide
authors.initials: M
authors.lastname: Ikeguchi
keywords: B7-H1; B7-H4; gastric cancer; macrophage; monocyte
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