Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma.

Abstract

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.

• Authors: Ilona Kryczek, Shuang Wei, Gefeng Zhu, Leann Myers, Peter Mottram, Pui Cheng, Lieping Chen, George Coukos, Weiping Zou
• Journal: Cancer research (Cancer Res) Vol. 67 Issue 18 Pg. 8900-5 (Sep 15 2007) ISSN: 0008-5472 [Print] United States
• PMID: 17875732 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• B7-1 Antigen
• Interleukin-6
• V-Set Domain-Containing T-Cell Activation Inhibitor 1
• VTCN1 protein, human
• Interleukin-10

Topics

• Antigen-Presenting Cells (immunology)
• B7-1 Antigen (biosynthesis, immunology)
• Female
• Humans
• Interleukin-10 (biosynthesis, immunology)
• Interleukin-6 (biosynthesis, immunology)
• Macrophages (immunology)
• Ovarian Neoplasms (immunology)
• T-Lymphocytes, Regulatory (immunology)
• V-Set Domain-Containing T-Cell Activation Inhibitor 1