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

Ilona Kryczek, Linhua Zou, Paulo Rodriguez, Gefeng Zhu, Shuang Wei, Peter Mottram, Michael Brumlik, Pui Cheng, Tyler J Curiel, Leann Myers, Andrew Lackner, Xavier Alvarez, Augusto Ochoa, Lieping Chen, Weiping Zou

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)871-881
Number of pages11
JournalJournal of Experimental Medicine
Volume203
Issue number4
DOIs
StatePublished - Apr 17 2006
Externally publishedYes

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Macrophages
Carcinoma
Population
Neoplasms
Ovarian Neoplasms
Tumor Microenvironment
T-Lymphocytes
Immunity
B7 Antigens
Cytokines
Arginase
Neoplasm Antigens
Nitric Oxide Synthase Type II
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Interleukin-10
Interleukin-6

ASJC Scopus subject areas

  • Immunology

Cite this

B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. / Kryczek, Ilona; Zou, Linhua; Rodriguez, Paulo; Zhu, Gefeng; Wei, Shuang; Mottram, Peter; Brumlik, Michael; Cheng, Pui; Curiel, Tyler J; Myers, Leann; Lackner, Andrew; Alvarez, Xavier; Ochoa, Augusto; Chen, Lieping; Zou, Weiping.

In: Journal of Experimental Medicine, Vol. 203, No. 4, 17.04.2006, p. 871-881.

Research output: Contribution to journalArticle

Kryczek, I, Zou, L, Rodriguez, P, Zhu, G, Wei, S, Mottram, P, Brumlik, M, Cheng, P, Curiel, TJ, Myers, L, Lackner, A, Alvarez, X, Ochoa, A, Chen, L & Zou, W 2006, 'B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma', Journal of Experimental Medicine, vol. 203, no. 4, pp. 871-881. https://doi.org/10.1084/jem.20050930
Kryczek, Ilona ; Zou, Linhua ; Rodriguez, Paulo ; Zhu, Gefeng ; Wei, Shuang ; Mottram, Peter ; Brumlik, Michael ; Cheng, Pui ; Curiel, Tyler J ; Myers, Leann ; Lackner, Andrew ; Alvarez, Xavier ; Ochoa, Augusto ; Chen, Lieping ; Zou, Weiping. / B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 4. pp. 871-881.
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