Deubiquitinases A20 and CYLD modulate costimulatory signaling via CD137 (4-1BB).

Abstract:

:TRAF2 dependent K63-polyubiquitinations have been recently shown to connect CD137 (4-1BB) stimulation to NF-κB activation. In a search of deubiquitinase enzymes (DUBs) that could regulate such a signaling route, A20 and CYLD were found to coimmunoprecipitate with CD137 and TRAF2 complexes. Indeed, overexpression of A20 or CYLD downregulated CD137-elicited ubiquitination of TRAF2 and TAK1 upon stimulation with agonist monoclonal antibodies. Moreover, overexpression of A20 or CYLD downregulated CD137-induced NF-κB activation in cultured cells and in gene-transferred hepatocytes in vivo, while silencing these deubiquitinases enhanced CD137 costimulation of primary human CD8 T cells. Therefore A20 and CYLD directly downregulate the signaling from a T and NK-cell costimulatory receptor under exploitation for cancer immunotherapy in clinical trials.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Azpilikueta A,Bolaños E,Lang V,Labiano S,Aznar MA,Etxeberria I,Teijeira A,Rodriguez-Ruiz ME,Perez-Gracia JL,Jure-Kunkel M,Zapata JM,Rodriguez MS,Melero I

doi

10.1080/2162402X.2017.1368605

subject

Has Abstract

pub_date

2017-09-21 00:00:00

pages

e1368605

issue

1

eissn

2162-4011

issn

2162-402X

pii

1368605

journal_volume

7

pub_type

杂志文章
  • Macrophages increase the resistance of pancreatic adenocarcinoma cells to gemcitabine by upregulating cytidine deaminase.

    abstract::Tumor-associated macrophages play a central role in tumor progression and metastasis. Macrophages can also promote the resistance of malignant cells to chemotherapy by stimulating the upregulation of cytidine deaminase, an intracellular enzyme that catabolizes the active form of gemcitabine. Targeting macrophage-depen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.27231

    authors: Amit M,Gil Z

    更新日期:2013-12-01 00:00:00

  • Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1β dependent upregulation of MYO3A gene in breast cancer cells.

    abstract::The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or "niche" interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cell...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1196299

    authors: Baghel KS,Tewari BN,Shrivastava R,Malik SA,Lone MU,Jain NK,Tripathi C,Kanchan RK,Dixit S,Singh K,Mitra K,Negi MP,Srivastava M,Misra S,Bhatt ML,Bhadauria S

    更新日期:2016-07-15 00:00:00

  • Trial watch: Oncolytic viruses for cancer therapy.

    abstract::Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterp...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24612

    authors: Vacchelli E,Eggermont A,Sautès-Fridman C,Galon J,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2013-06-01 00:00:00

  • Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia.

    abstract::Natural killer (NK)-cell count is predictive of chronic lymphoid leukemia (CLL) disease progression and their dysfunction is well documented, but the etiology of this is currently lacking. CLL cells have been shown to over-express HLA-E, the natural ligand for NKG2A expressed on NK-cells that generates a distinct nega...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1226720

    authors: McWilliams EM,Mele JM,Cheney C,Timmerman EA,Fiazuddin F,Strattan EJ,Mo X,Byrd JC,Muthusamy N,Awan FT

    更新日期:2016-09-09 00:00:00

  • Immunogenic cell death in a combined synergic gene- and immune-therapy against cancer.

    abstract::It was previously demonstrated that engineered mesenchymal stem cells (MSCs) which express a high level of a very efficient modified gene CYP2B6* (CYP2B6TM-RED) acting as a suicide gene (MSC-2B6*) in combination with cyclophosphamide (CPA) constitute a powerful cell/gene therapy approach for solid tumors. In murine mo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1667743

    authors: Nayagom B,Amara I,Habiballah M,Amrouche F,Beaune P,de Waziers I

    更新日期:2019-09-27 00:00:00

  • A novel facet of tumor suppression by p53: Induction of tumor immunogenicity.

    abstract::Pharmacological reactivation of the p53 tumor suppressor is a promising strategy for anti-cancer therapy due to its high potential to elicit apoptosis or growth arrest in cancer cells. Recently we uncovered the mechanism of activation of the innate immune response by p53 upon its activation by small molecules. ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19409

    authors: Li H,Lakshmikanth T,Carbone E,Selivanova G

    更新日期:2012-07-01 00:00:00

  • Trial Watch: Peptide vaccines in cancer therapy.

    abstract::Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthus...

    journal_title:Oncoimmunology

    pub_type: 评审

    doi:10.4161/onci.26621

    authors: Aranda F,Vacchelli E,Eggermont A,Galon J,Sautès-Fridman C,Tartour E,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2013-12-01 00:00:00

  • Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells.

    abstract::Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1268309

    authors: Cui B,Lu S,Lai L,Xie Y,He J,Xue Y,Xiao P,Pan T,Chen L,Liu Y,Cao X,Wang Q

    更新日期:2017-01-20 00:00:00

  • Primary sterile necrotic cells fail to cross-prime CD8(+) T cells.

    abstract::Necrotic cells are known to activate the innate immune system and trigger inflammation by releasing damage associated molecular patterns (DAMPs). However, how necrotic cells influence the induction of antigen-specific CD8(+) T cell-mediated adaptive immune responses under sterile conditions, in the absence of pathogen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21098

    authors: Gamrekelashvili J,Ormandy LA,Heimesaat MM,Kirschning CJ,Manns MP,Korangy F,Greten TF

    更新日期:2012-10-01 00:00:00

  • Tumor vascularity in ovarian cancer: T cells need breathing room.

    abstract::Tumor-infiltrating lymphocytes (TILs) are crucial for effective antitumor responses. However, hypoxia can skew T-cell differentiation and function, thereby perturbing TILs. We have demonstrated that TILs and their immune function are associated with tumor vascularization. These features are prognostic for improved dis...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28272

    authors: Neilson D,MacPherson S,Townsend KN,Lum JJ

    更新日期:2014-04-08 00:00:00

  • Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study.

    abstract::Objective:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in ot...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1502905

    authors: Pedersen M,Westergaard MCW,Milne K,Nielsen M,Borch TH,Poulsen LG,Hendel HW,Kennedy M,Briggs G,Ledoux S,Nøttrup TJ,Andersen P,Hasselager T,Met Ö,Nelson BH,Donia M,Svane IM

    更新日期:2018-09-26 00:00:00

  • PD-L1 co-stimulation, ligand-induced TCR down-modulation and anti-tumor immunotherapy.

    abstract::PD-1 engagement on the surface of effector T cells strongly suppresses their cytotoxic function, which constitutes a major obstacle for T cell-mediated anti-tumor activities. Surprisingly, PD-1 is strongly upregulated in T cells, engaging its ligand PD-L1 during antigen presentation. However, our recent published data...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.1.1.17824

    authors: Karwacz K,Arce F,Bricogne C,Kochan G,Escors D

    更新日期:2012-01-01 00:00:00

  • TRAIL-receptor 1 IgM antibodies strongly induce apoptosis in human cancer cells in vitro and in vivo.

    abstract::Agonistic tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-receptor-specific antibodies are attractive antitumor therapeutics. Recently, our group has generated several human monoclonal antibodies (mAbs) to TRAIL-receptor-1 (TRAIL-R1) (TR1-IgGs) using ISAAC technology. However, these TR1-IgGs did ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1131380

    authors: Piao X,Ozawa T,Hamana H,Shitaoka K,Jin A,Kishi H,Muraguchi A

    更新日期:2016-05-04 00:00:00

  • Trial Watch: Toll-like receptor agonists for cancer therapy.

    abstract::Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitat...

    journal_title:Oncoimmunology

    pub_type: 评审

    doi:10.4161/onci.25238

    authors: Vacchelli E,Eggermont A,Sautès-Fridman C,Galon J,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2013-08-01 00:00:00

  • Non-V delta 2 gamma delta T lymphocytes as effectors of cancer immunotherapy.

    abstract::Gamma delta T cells (γδT) are potent mediators of antitumor cytotoxicity and have shown promising efficacy in early phase clinical trials. Most is known about the tumoricidal properties of cells bearing the Vδ2 T cell receptor chain, but recent studies have demonstrated that cells with the Vδ1 chain and those with nei...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/2162402X.2014.973808

    authors: Fisher J,Kramer AM,Gustafsson K,Anderson J

    更新日期:2014-12-23 00:00:00

  • Hormesis in cancer immunology: Does the quantity of an immune reactant matter?

    abstract::We recently reported that tumor-directed antibodies could either stimulate, or inhibit, tumor progression, dependent upon the dosage used. The narrow range over which this immune response curve (IRC) occurs is surprising. Here we discuss features of the IRC, the mechanisms identified so far, and the potential clinical...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.29312

    authors: Pearce OM,Läubli H,Bui J,Varki A

    更新日期:2014-06-25 00:00:00

  • Novel treatment strategy with autologous activated and expanded natural killer cells plus anti-myeloma drugs for multiple myeloma.

    abstract::This proof-of-concept single-arm open-label phase I clinical trial (NCT02481934) studied the safety and efficacy of multiple infusions of activated and expanded natural killer (NKAE) cells in combination with anti-myeloma drugs in multiple myeloma patients. It included five patients with relapsed or refractory MM who ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1250051

    authors: Leivas A,Perez-Martinez A,Blanchard MJ,Martín-Clavero E,Fernández L,Lahuerta JJ,Martinez-Lopez J

    更新日期:2016-11-22 00:00:00

  • mRNA-transfected dendritic cell vaccine in combination with metronomic cyclophosphamide as treatment for patients with advanced malignant melanoma.

    abstract:INTRODUCTION:Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen o...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1207842

    authors: Borch TH,Engell-Noerregaard L,Zeeberg Iversen T,Ellebaek E,Met Ö,Hansen M,Andersen MH,Thor Straten P,Svane IM

    更新日期:2016-07-08 00:00:00

  • Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer.

    abstract::A fluorescence-based, high-resolution imaging approach was used to visualize longitudinally the cellular events unfolding during T cell-mediated tumor destruction. The dynamic interplay of T cells, cancer cells, cancer antigen loss variants, and stromal cells-all color-coded in vivo-was analyzed in established, solid ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26677

    authors: Schietinger A,Arina A,Liu RB,Wells S,Huang J,Engels B,Bindokas V,Bartkowiak T,Lee D,Herrmann A,Piston DW,Pittet MJ,Lin PC,Zal T,Schreiber H

    更新日期:2013-11-01 00:00:00

  • Targeted overexpression of prostacyclin synthase inhibits lung tumor progression by recruiting CD4+ T lymphocytes in tumors that express MHC class II.

    abstract::Lung-specific overexpression of prostacyclin synthase (PGIS) decreases tumor initiation in murine lung cancer models. Prostacyclin analogs prevent lung tumor formation in mice and reverse bronchial dysplasia in former smokers. However, the effect of prostacyclin on lung cancer progression has not been well studied. We...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1423182

    authors: Li HY,McSharry M,Walker D,Johnson A,Kwak J,Bullock B,Neuwelt A,Poczobutt JM,Sippel TR,Keith RL,Weiser-Evans MCM,Clambey E,Nemenoff RA

    更新日期:2018-02-13 00:00:00

  • Instruction of myeloid cells by the tumor microenvironment: Open questions on the dynamics and plasticity of different tumor-associated myeloid cell populations.

    abstract::The versatility and plasticity of myeloid cell polarization/differentiation has turned out to be crucial in health and disease, and has become the subject of intense investigation during the last years. On one hand, myeloid cells provide a critical contribution to tissue homeostasis and repair. On the other hand, myel...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21566

    authors: Schouppe E,De Baetselier P,Van Ginderachter JA,Sarukhan A

    更新日期:2012-10-01 00:00:00

  • Trial watch: Tumor-targeting monoclonal antibodies for oncological indications.

    abstract::An expanding panel of monoclonal antibodies (mAbs) that specifically target malignant cells or intercept trophic factors delivered by the tumor stroma is now available for cancer therapy. These mAbs can exert direct antiproliferative/cytotoxic effects as they inhibit pro-survival signal transduction cascades or activa...

    journal_title:Oncoimmunology

    pub_type: 评审

    doi:10.4161/2162402X.2014.985940

    authors: Vacchelli E,Pol J,Bloy N,Eggermont A,Cremer I,Fridman WH,Galon J,Marabelle A,Kohrt H,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2015-02-03 00:00:00

  • Rehmannia glutinosa polysaccharide induces toll-like receptor 4 dependent spleen dendritic cell maturation and anti-cancer immunity.

    abstract::Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 m...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1325981

    authors: Xu L,Kwak M,Zhang W,Zeng L,Lee PC,Jin JO

    更新日期:2017-05-12 00:00:00

  • Mammaglobin-A is a target for breast cancer vaccination.

    abstract::We recently completed a phase 1 clinical trial demonstrating the safety of a mammaglobin-A DNA vaccine in patients with metastatic breast cancer. We are currently enrolling patients with early stage breast cancer in a phase 1b clinical trial. The mammaglobin-A DNA vaccine will be administered concurrently with neoadju...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1069940

    authors: Kim SW,Goedegebuure P,Gillanders WE

    更新日期:2016-02-26 00:00:00

  • From cell biology to immunology: Controlling metastatic progression of cancer via microRNA regulatory networks.

    abstract::Recently, the study of microRNAs has expanded our knowledge of the fundamental processes of cancer biology and the underlying mechanisms behind tumor metastasis. Extensive research in the fields of microRNA and its novel mechanisms of actions against various cancers has more recently led to the trial of a first cancer...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2016.1230579

    authors: Park JH,Theodoratou E,Calin GA,Shin JI

    更新日期:2016-09-09 00:00:00

  • Tumor-infiltrating follicular helper T cells: The new kids on the block.

    abstract::By analyzing CD4+ lymphocytes in human breast carcinomas, we have recently uncovered the presence of follicular helper T cells in lesions exhibiting an extensive immune infiltrate. The presence of these specialized CD4+ T cells, which localize to the germinal centers of peritumoral tertiary lymphoid structures found i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26066

    authors: Gu-Trantien C,Willard-Gallo K

    更新日期:2013-10-01 00:00:00

  • Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes.

    abstract::T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-r...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26014

    authors: Sittig SP,Køllgaard T,Grønbæk K,Idorn M,Hennenlotter J,Stenzl A,Gouttefangeas C,Thor Straten P

    更新日期:2013-09-01 00:00:00

  • Chemokines and chemokine receptors required for optimal responses to anticancer chemotherapy.

    abstract::Depending on tumor type, stage and immunological contexture, the inhibition of chemokines or their receptors may yield positive or deleterious effects on disease progression. We have recently demonstrated in several murine models of anthracycline-based chemotherapy that the inhibition of chemokine (C-C motif) ligand 2...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.27663

    authors: Ma Y,Adjemian S,Galluzzi L,Zitvogel L,Kroemer G

    更新日期:2014-01-01 00:00:00

  • Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy.

    abstract::Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antit...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1188244

    authors: Azuma M,Takeda Y,Nakajima H,Sugiyama H,Ebihara T,Oshiumi H,Matsumoto M,Seya T

    更新日期:2016-05-19 00:00:00

  • EBV infection determines the immune hallmarks of plasmablastic lymphoma.

    abstract::Despite recent therapeutic progress, plasmablastic lymphoma (PBL), a distinct entity of high grade B cell lymphoma, is still an aggressive lymphoma with adverse prognosis. PBL commonly occurs in patients with HIV infection and PBL cells frequently express Epstein Barr virus (EBV) genome with type I latency. Occasional...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1486950

    authors: Gravelle P,Péricart S,Tosolini M,Fabiani B,Coppo P,Amara N,Traverse-Gléhen A,Van Acker N,Brousset P,Fournie JJ,Laurent C

    更新日期:2018-07-30 00:00:00