This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kryczek, I. Articles by Zou, W. Search for Related Content PubMed PubMed Citation Articles by Kryczek, I. Articles by Zou, W.

Relationship between B7-H4, Regulatory T Cells, and Patient Outcome in Human Ovarian Carcinoma

¹ Department of Surgery, University of Michigan, Ann Arbor, Michigan; ² Departments of Dermatology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; ³ Tulane University Health Science Center, New Orleans, Louisiana; and ⁴ Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, Pennsylvania

Requests for reprints: Weiping Zou, University of Michigan School of Medicine, C560B MSRB II, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0669. Phone: 734-763-6402; Fax: 734-763-0143; E-mail: wzou{at}umich.edu.

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. [Cancer Res 2007;67(18):8901–05]

This article has been cited by other articles:

				W. Wang, R. Lau, D. Yu, W. Zhu, A. Korman, and J. Weber PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+CD25Hi regulatory T cells Int. Immunol., September 1, 2009; 21(9): 1065 - 1077. [Abstract] [Full Text] [PDF]

				I. Kryczek, R. Liu, G. Wang, K. Wu, X. Shu, W. Szeliga, L. Vatan, E. Finlayson, E. Huang, D. Simeone, et al. FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease Cancer Res., May 1, 2009; 69(9): 3995 - 4000. [Abstract] [Full Text] [PDF]