Article: article from journal or magazin.
Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma.
Publication types: Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
B7-H4 is a recently identified B7 family member. We previously showed that ovarian tumor and associated macrophages expressed B7-H4; tumor B7-H4+ macrophages and CD4+CD25+FOXP3+ regulatory T cells (Treg cells) suppressed tumor-associated antigen-specific T-cell immunity. To determine the pathologic relationship between B7-H4, macrophages, and Treg cells in the tumor environment, in addition to Treg cell numbers, we quantified B7-H4 expression in the tumor and tumor-associated macrophages in 103 patients with ovarian carcinoma. We observed that the intensity of B7-H4 expression in macrophages was significantly correlated with Treg cell numbers in the tumor. Further, both Treg cells and macrophage B7-H4, but not tumor B7-H4, were negatively associated with patient outcome. Tumor Treg cells enabled macrophages to spontaneously produce interleukin (IL)-10 and IL-6. Tumor macrophages stimulated B7-H4 expression in an autocrine manner through IL-10 and IL-6. Our previous work showed that tumor-associated macrophages spontaneously produced chemokine CCL22 to mediate Treg cell trafficking into tumor, and Treg cells induced B7-H4 on antigen-presenting cells (APC) including macrophages. Altogether, our data support the concept that there is a mechanistic interaction between Treg cells and macrophage, and that Treg cells may convey the suppressive activity to APCs through B7-H4 induction in human ovarian cancer.
Antigen-Presenting Cells/immunology, Antigens, CD80/biosynthesis, Antigens, CD80/immunology, Female, Humans, Interleukin-10/biosynthesis, Interleukin-10/immunology, Interleukin-6/biosynthesis, Interleukin-6/immunology, Macrophages/immunology, Ovarian Neoplasms/immunology, T-Lymphocytes, Regulatory/immunology, V-Set Domain-Containing T-Cell Activation Inhibitor 1
Web of science
Last modification date