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

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.

• Publication year

  2006

• Venue

  Journal of Experimental Medicine

• Publication date

  2006-04-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/jem.20050930PMID 16606666PMCID 2118300
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• IL-6 and IL-10 stimulate macrophage B7-H4 expression, whereas granulocyte/macrophage colony-stimulating factor and IL-4 inhibit it.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• Blocking B7-H4, but not arginase, inducible nitric oxide synthase, or B7-H1, restores the T cell-stimulating capacity of tumor macrophages and contributes to tumor regression in vivo.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• B7-H4+ tumor macrophages suppress tumor-associated antigen-specific T cell immunity.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• Primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review

• b7-h4

  protein, immune checkpoint molecule

  A B7 family immune-regulatory molecule examined as a checkpoint marker on ovarian tumor cells and macrophages.

  Aliases: B7H4, B7 family molecule B7-H4

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• granulocyte/macrophage colony-stimulating factor

  cytokine, protein

  A cytokine used as a comparator for regulating macrophage B7-H4 expression.

  Aliases: GM-CSF

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• il-10

  cytokine, protein

  A cytokine present in the ovarian tumor microenvironment and tested for effects on macrophage B7-H4 expression.

  Aliases: interleukin-10

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• il-4

  cytokine, protein

  A cytokine used as a comparator for regulating macrophage B7-H4 expression.

  Aliases: interleukin-4

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• il-6

  cytokine, protein

  A cytokine present in the ovarian tumor microenvironment and tested for effects on macrophage B7-H4 expression.

  Aliases: interleukin-6

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• primary ovarian tumor cells

  cell type, cancer cell

  Malignant cells isolated from the primary ovarian carcinoma specimens analyzed in the study.

  Aliases: ovarian tumor cells

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• tumor-associated antigen-specific t cell immunity

  immune response, outcome

  T cell responses directed against antigens associated with the tumor.

  Aliases: tumor antigen-specific T cell immunity, antigen-specific T cell immunity

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review
• tumor macrophages

  cell type, immune cell

  Macrophages present within the ovarian tumor stroma or tumor microenvironment.

  Aliases: tumor-associated macrophages, TAMs

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewq (76h6bfydm6) review

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