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B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.


ABSTRACT: Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. In contrast, granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4 makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer. B7-H4 expression represents a critical checkpoint in determining host responses to dysfunctional cytokines in ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may represent novel strategies to enhance T cell tumor immunity in cancer.

SUBMITTER: Kryczek I 

PROVIDER: S-EPMC2118300 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.

Kryczek Ilona I   Zou Linhua L   Rodriguez Paulo P   Zhu Gefeng G   Wei Shuang S   Mottram Peter P   Brumlik Michael M   Cheng Pui P   Curiel Tyler T   Myers Leann L   Lackner Andrew A   Alvarez Xavier X   Ochoa Augusto A   Chen Lieping L   Zou Weiping W  

The Journal of experimental medicine 20060410 4


Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-  ...[more]

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