title: Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response.
abstract: 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.
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Qu
authors.forename: Xu-Qin
authors.initials: XQ
authors.lastname: Chen
authors.forename: Xue-Guang
authors.initials: XG
authors.lastname: Zhang
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Huang
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019139:Tumor Escape / Q000276:immunology
chemical_list: D060887:B7 Antigens; C486038:Cd276 protein, mouse