title: Effects of lung cancer cell-associated B7-H1 on T-cell proliferation in vitro and in vivo.
abstract: B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.
authors.affiliation: Soochow University, Soochow University, Department of Cardiothoracic Surgery, Jiangsu , China, Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: Soochow University, Soochow University, Department of Cardiothoracic Surgery, Jiangsu , China, Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: H T
authors.initials: HT
authors.lastname: Huang
authors.affiliation: Soochow University, Soochow University, Department of Cardiothoracic Surgery, Jiangsu , China, Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: W J
authors.initials: WJ
authors.lastname: Hang
authors.affiliation: Soochow University, Soochow University, Department of Cardiothoracic Surgery, Jiangsu , China, Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: L B
authors.initials: LB
authors.lastname: Pan
authors.affiliation: Soochow University, Soochow University, Department of Cardiothoracic Surgery, Jiangsu , China, Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: H T
authors.initials: HT
authors.lastname: Ma
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000032:analysis* / Q000037:antagonists & inhibitors; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D013160:Splenic Neoplasms / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D060890:B7-H1 Antigen