Dataset Information

T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-? Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma.

ABSTRACT: USP15 is a deubiquitinase that negatively regulates activation of naive CD4(+) T cells and generation of IFN-?-producing T helper 1 (Th1) cells. USP15 deficiency in mice promotes antitumor T cell responses in a transplantable cancer model; however, it has remained unclear how deregulated T cell activation impacts primary tumor development during the prolonged interplay between tumors and the immune system. Here, we find that the USP15-deficient mice are hypersensitive to methylcholantrene (MCA)-induced fibrosarcomas. Excessive IFN-? production in USP15-deficient mice promotes expression of the immunosuppressive molecule PD-L1 and the chemokine CXCL12, causing accumulation of T-bet(+) regulatory T cells and CD11b(+)Gr-1(+) myeloid-derived suppressor cells at tumor site. Mixed bone marrow adoptive transfer studies further reveals a T cell-intrinsic role for USP15 in regulating IFN-? production and tumor development. These findings suggest that T cell intrinsic USP15 deficiency causes excessive production of IFN-?, which promotes an immunosuppressive tumor microenvironment during MCA-induced primary tumorigenesis.

SUBMITTER: Zou Q

PROVIDER: S-EPMC4691552 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-γ Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma.

Zou Qiang Q Jin Jin J Xiao Yichuan Y Zhou Xiaofei X Hu Hongbo H Cheng Xuhong X Kazimi Nasser N Ullrich Stephen E SE Sun Shao-Cong SC

Cell reports 20151210 11

USP15 is a deubiquitinase that negatively regulates activation of naive CD4(+) T cells and generation of IFN-γ-producing T helper 1 (Th1) cells. USP15 deficiency in mice promotes antitumor T cell responses in a transplantable cancer model; however, it has remained unclear how deregulated T cell activation impacts primary tumor development during the prolonged interplay between tumors and the immune system. Here, we find that the USP15-deficient mice are hypersensitive to methylcholantrene (MCA)- ...[more]

PMID: 26686633

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Dataset Information

T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-? Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma.

Publications

T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-γ Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma.

Similar Datasets

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