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

• Published in: Experimental cell research Vol. 319; no. 1; pp. 96 - 102
• Main Authors: Chen, Cheng, Shen, Yu, Qu, Qiu-Xia, Chen, Xu-Qin, Zhang, Xue-Guang, Huang, Jian-An
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2013; Elsevier BV
• Subjects: Animals; B7 Antigens - biosynthesis; B7 Antigens - genetics; B7 Antigens - physiology; B7-H3; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - metabolism; Carcinoma, Lewis Lung - pathology; CD80 antigen; Cell Line, Tumor; Circuits; Coculture Techniques; Female; Gene expression; Immune response; Immunological tolerance; Immunology; Inflammation; Interleukin 10; Lung cancer; Lung carcinoma; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphocytes T; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - pathology; Mice; Mice, Inbred C57BL; mRNA; Neoplasm Transplantation - methods; Solid tumors; Stroma; T cell; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Transformation; Tumor cell lines; Tumor cells; Tumor Escape - immunology; Tumor-associated macrophage; Tumors; B7-H3; Tumor-associated macrophage; Lung cancer; T cell
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2012.09.006

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.