title: Induced expression of B7-H4 on the surface of lung cancer cell by the tumor-associated macrophages: a potential mechanism of immune escape.
abstract: B7-homolog 4 (B7-H4), a recently identified homolog of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H4 in lung cancer in vitro and in vivo. Although a lung cancer cell line constitutively expressed B7-H4 mRNA and protein in plasma, primary tumor cell isolated from the transplanted lung carcinoma model expressed B7-H4 on the surface. Interestingly, in transplanted lung carcinoma model, the expression of membrane-bound B7-H4 in tumor cells was increased as prolonging of tumor transformation. Exposure to tumor-associated macrophages strongly induced membrane-bound B7-H4 expression on the lung cancer cell line. To elucidate the functional significance of lung cancer-related B7-H4 expression, we performed co-culture experiments of lung cancer cell with allo-reactive T cells. Lung cancer-related B7-H4 was identified as a strong inhibitor of T-cell effect. Furthermore, B7-H4 mAb had an ability to inhibit tumor growth in vivo. B7-H4 expression may thus significantly influence the outcome of T-cell tumor cell interactions and TAM induced membrane-bound B7-H4 on the lung cancer cell represents a novel mechanism by which lung cancer cells evade immune recognition and destruction.
authors: Respiratory Department, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors: Cheng
authors: C
authors: Chen
authors: Qiu-Xia
authors: QX
authors: Qu
authors: Yu
authors: Y
authors: Shen
authors: Chuan-Yong
authors: CY
authors: Mu
authors: Yi-Bei
authors: YB
authors: Zhu
authors: Xue-Guang
authors: XG
authors: Zhang
authors: Jian-An
authors: JA
authors: Huang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; C556062:IL10 protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475824:Vtcn1 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma