Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response

Exp Cell Res. 2013 Jan 1;319(1):96-102. doi: 10.1016/j.yexcr.2012.09.006. Epub 2012 Sep 19.


Macrophages are the prominent components of solid tumors and have complex dual functions in their interaction with cancer cells. Strong evidence suggests that TAM is a part of inflammatory circuits that promote tumor progression. B7-homologue 3 (B7-H3), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. Here, we showed that a fraction of macrophages in tumor stroma expressed surface B7-H3 molecule. Normal macrophages, which did not express B7-H3, would be induced expressing B7-H3 molecule when culturing with tumor cell. Although a lung cancer cell line constitutively expressed B7-H3 mRNA and protein in plasma, primary tumor cell isolated from the transplanted lung carcinoma model expressed B7-H3 on the surface. Interestingly, in transplanted lung carcinoma model, the expression of membrane-bound B7-H3 in tumor cells was increased as prolonging of tumor transformation. In support, IL-10 released from TAM could stimulate cancer cell expression of membrane bound B7-H3. Furthermore, Lung cancer and TAM-related B7-H3 was identified as a strong inhibitor of T-cell effect and influenced the outcome of T cell immune response. In conclusion, TAM-tumor cell interaction-induced membrane-bound B7-H3 represents a novel immune escape mechanism which links the pro-inflammatory response to immune tolerance in the tumor milieu.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7 Antigens / biosynthesis*
  • B7 Antigens / genetics*
  • B7 Antigens / physiology
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / metabolism*
  • Carcinoma, Lewis Lung / pathology
  • Cell Line, Tumor
  • Coculture Techniques
  • Female
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism*
  • Macrophages, Alveolar / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation / methods
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Tumor Escape / immunology


  • B7 Antigens
  • Cd276 protein, mouse