Immune cell expression of TGFβ1 in cancer with lymphoid stroma: dendritic cell and regulatory T cell contact

Abstract

Although cancer tissue generally shows limited immune responses, some cancers abound with lymphocytes, which generally show favorable prognosis. These cancers, despite their rarity, are important in analyzing immune responses in cancer tissue. Transforming growth factor β1 (TFGβ1) is a multifunctional cytokine, generally having an immunosuppressive function. The present study analyzes the in situ TGFβ1 expression in 23 cases of lymphocyte-rich gastric carcinomas (Ly-rich GCs) using immunohistochemistry and in situ hybridization. Immunohistochemistry revealed that latency-associated peptide (LAP) of TGFβ1 was localized in mainly immune cells in all cases, which was more abundant than in control GCs. Expression of LAP by cancer cells was only focal. In situ hybridization also confirmed abundant TGFβ1 mRNA expression in the lymphoid stroma. Double immunofluorescent microscopy identified LAP⁺ cells as macrophages, dendritic cells, and part of T cells. Close cell-to-cell contact was observed between LAP⁺ dendritic-shaped cells and FoxP3⁺ regulatory T cells (T_reg cells). Mature dendritic cells in Ly-rich GCs expressed LAP more frequently than those in the secondary lymphoid organs. Our data revealed abundant expression of TGFβ1 in immune cells with contact to T_reg cells in lymphoid stroma, which is consistent with the notion that TGFβ1 is one of the immunosuppressive factors in cancer stroma.

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