title: Immune evasion of mantle cell lymphoma: expression of B7-H1 leads to inhibited T-cell response to and killing of tumor cells.
abstract: Clinical trials of immunotherapy in mantle cell lymphoma have not yet delivered desirable results, partly because of the inhibitory machinery of the tumor and its microenvironment. Here we investigated the role of B7-H1, a member of the B7 family of co-stimulatory/co-inhibitory ligands, in mantle cell lymphoma-mediated immunosuppression. Allogeneic CD3(+), CD4(+) and CD8(+) T cells were purified and co-cultured with irradiated mantle cell lymphoma cells. Mantle cell lymphoma-reactive T-cell lines from HLA-A*0201(+) healthy blood donors were generated after in vitro restimulation, and were subjected to functional tests. We found that B7-H1 expressed on mantle cell lymphoma cells was able to inhibit T-cell proliferation induced by the tumor cells, impair the generation of antigen-specific T-cell responses, and render mantle cell lymphoma cells resistant to T-cell-mediated cytolysis. Blocking or knocking down B7-H1 on mantle cell lymphoma cells enhanced T-cell responses and restored tumor-cell sensitivity to T-cell-mediated killing in vitro and in vivo. Knocking down B7-H1 on mantle cell lymphoma cells primed more CD4(+) or CD8(+) memory effector T cells. Our study demonstrates for the first time that lymphoma cell-expressed B7-H1 may lead to the suppression of host anti-tumor immune responses in mantle cell lymphoma and targeting tumor cell B7-H1 may represent a novel approach to improve the efficacy of immunotherapy in patients with mantle cell lymphoma.
authors.affiliation: Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Qian
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.forename: Hanying
authors.initials: H
authors.lastname: Bao
authors.forename: Donghua
authors.initials: D
authors.lastname: He
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Sattva
authors.initials: S
authors.lastname: Neelapu
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D020522:Lymphoma, Mantle-Cell / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019139:Tumor Escape / Q000502:physiology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human