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 intestinal inflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC through suppression of inflammatory cytokines in intestinal epithelial cells (IECs). IL-27Rα (WSX-1) deficiency promotes the CAC development in mice, which is driven by enhanced tumor cell proliferation, more intensive myeloid-derived suppressor cells (MDSC) accumulation in colon lamina propria and higher level of inflammatory cytokines and chemokines in IECs. The levels of IL-6, TNF-α, GM-CSF and CXCL1 triggered in vitro by toll-like receptor ligands are significantly upregulated in IECs from WSX-1 KO mice. Removal of commensal microorganism through antibiotic treatment in mice to eliminate TLR ligands deprives the protective function of IL-27 on CAC tumor growth. Thus, IL-27 suppresses CAC formation through an anti-inflammation mechanism targeting IECs and in turn resists the tumorigenesis. Hence, our study explained how IL-27 exerts its anti-inflammatory function on epithelial cells to fight against chronic-inflammation-associated cancer, which might provide new insights on the potential therapeutic strategies for cancer.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

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

doi

10.1080/2162402X.2016.1268309

subject

Has Abstract

pub_date

2017-01-20 00:00:00

pages

e1268309

issue

2

eissn

2162-4011

issn

2162-402X

pii

1268309

journal_volume

6

pub_type

杂志文章
  • Bcl-2: Live and let die.

    abstract::Recent findings from our laboratory provide the first indication that overexpression of Bcl-2 in Eµ-myc transgenic cells enhances tumor immunosurveillance by inducing NKG2D ligands. Initial evidence suggests that this model is relevant to human patients. Thus, antitumor therapies that target Bcl-2 harbor the risk of r...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19536

    authors: Putz EM,Schuster C,Sexl V

    更新日期:2012-08-01 00:00:00

  • Strategies for purging CD96+ stem cells in vitro and in vivo: New avenues for autologous stem cell transplantation in acute myeloid leukemia.

    abstract::The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse. The selective elimination of CD96+ AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24500

    authors: Staudinger M,Humpe A,Gramatzki M

    更新日期:2013-06-01 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

  • Differential potency of regulatory T cell-mediated immunosuppression in kidney tumors compared to subcutaneous tumors.

    abstract::In many cancers, regulatory T cells (Treg) play a crucial role in suppressing the effector immune response thereby permitting tumor development. Indeed, in mouse models, their depletion can promote the regression of tumors of various origins, including renal cell carcinoma when located subcutaneous (SC). In the presen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.963395

    authors: Devaud C,Westwood JA,Teng MW,John LB,Yong CS,Duong CP,Smyth MJ,Darcy PK,Kershaw MH

    更新日期:2014-12-21 00:00:00

  • The STING agonist DMXAA triggers a cooperation between T lymphocytes and myeloid cells that leads to tumor regression.

    abstract::Regressing tumors are usually associated with a large immune infiltrate, but the molecular and cellular interactions that govern a successful anti-tumor immunity remain elusive. Here, we have triggered type I Interferon (IFN) signaling in a breast tumor model (MMTV-PyMT) using 5,6-dimethylxanthenone-4-acetic acid (DMX...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1346765

    authors: Weiss JM,Guérin MV,Regnier F,Renault G,Galy-Fauroux I,Vimeux L,Feuillet V,Peranzoni E,Thoreau M,Trautmann A,Bercovici N

    更新日期:2017-07-07 00:00:00

  • Procarcinogenic regulatory T cells in microbial-induced colon cancer.

    abstract::Regulatory T cell (Treg) promote IL-17-mediated colon tumorigenesis in multiple intestinal neoplasia (Min) mice colonized with enterotoxigenic Bacteroides fragilis (ETBF). Although they retain their immunosuppressive function, mucosal Treg are instrumental to initiate ETBF-triggered IL-17 colitis by limiting the avail...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1118601

    authors: Geis AL,Housseau F

    更新日期:2015-12-21 00:00:00

  • NY-ESO-1 expression in sarcomas: A diagnostic marker and immunotherapy target.

    abstract::NY-ESO-1 (CTAG 1B) is highly expressed in the majority of synovial sarcomas and myxoid/round cell liposarcomas as well as in a subset of melanomas, but only rarely in other mesenchymal tumors. This points to a potential for using NY-ESO-1 in the differential diagnosis of these lesions. Furthermore, promising results h...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21059

    authors: Lai JP,Rosenberg AZ,Miettinen MM,Lee CC

    更新日期:2012-11-01 00:00:00

  • Bone marrow provides an environment that prevents suppression of therapeutic graft-vs.-tumor immunity by regulatory T cells.

    abstract::Regulatory T cells (Tregs) can prevent graft-vs.-host disease as induced by the infusion of donor lymphocytes to cancer patients, but often they also suppress therapeutic antitumor immunity. We discuss an exception to this phenomenon, exemplifying how the milieu provided by the bone marrow may neutralize Tregs to allo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24659

    authors: Guichelaar T,Mutis T

    更新日期:2013-07-01 00:00:00

  • A pipeline for identification and validation of tumor-specific antigens in a mouse model of metastatic breast cancer.

    abstract::Cancer immunotherapy continues to make headway as a treatment for advanced stage tumors, revealing an urgent need to understand the fundamentals of anti-tumor immune responses. Noteworthy is a scarcity of data pertaining to the breadth and specificity of tumor-specific T cell responses in metastatic breast cancer. Aut...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1685300

    authors: DeVette CI,Gundlapalli H,Lai SA,McMurtrey CP,Hoover AR,Gurung HR,Chen WR,Welm AL,Hildebrand WH

    更新日期:2019-11-29 00:00:00

  • Of microspheres and microbes: A double-hit strategy for cancer immunotherapy.

    abstract::Efficient immunotherapy relies on the rapid generation of elevated amounts of cancer-specific T lymphocytes. We have recently demonstrated that both rapid and potent tumor-targeting immune responses can be induced with a heterologous prime-boost regimen consisting of poly-lactic co-glycolic acid (PLGA) microsphere-bas...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.27873

    authors: Brinkhoff B,Wirth TC

    更新日期:2014-02-14 00:00:00

  • Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma.

    abstract::Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have shown activity in patients with advanced renal cell carcinoma (RCC). However, the role of PD-1 expression in tumor-infiltrating lymphocytes (TILs) as a biomarker for poor outcome is not clear. In this study, we evaluated the prognostic value of T...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1413519

    authors: Kim KS,Sekar RR,Patil D,Dimarco MA,Kissick HT,Bilen MA,Osunkoya AO,Master VA

    更新日期:2018-01-10 00:00:00

  • BRAF V600E mutation correlates with suppressive tumor immune microenvironment and reduced disease-free survival in Langerhans cell histiocytosis.

    abstract::Langerhans cell histiocytosis (LCH) is a neoplasm of myeloid origin characterized by a clonal proliferation of CD1a(+)/CD207(+) dendritic cells. Recurrent BRAF V600E mutation has been reported in LCH. In the present report, we confirm the feasibility of the high-specificity monoclonal antibody VE1 for detecting BRAF V...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1185582

    authors: Zeng K,Wang Z,Ohshima K,Liu Y,Zhang W,Wang L,Fan L,Li M,Li X,Wang Y,Yu Z,Yan Q,Guo S,Wei J,Guo Y

    更新日期:2016-06-14 00:00:00

  • Why do human B cells secrete granzyme B? Insights into a novel B-cell differentiation pathway.

    abstract::B cells are generally believed to operate as producers of high affinity antibodies to defend the body against microorganisms, whereas cellular cytotoxicity is considered as an exclusive prerogative of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In conflict with this dogma, recent studies have demonst...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.22354

    authors: Hagn M,Jahrsdörfer B

    更新日期:2012-11-01 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

  • A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice.

    abstract::Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1421890

    authors: Choi JH,Kim KH,Roh KH,Jung H,Lee A,Lee JY,Song JY,Park SJ,Kim I,Lee WS,Seo SK,Choi IW,Fu YX,Yea SS,Park S

    更新日期:2018-01-16 00:00:00

  • Acute myeloid leukemia and NK cells: two warriors confront each other.

    abstract::Acute myeloid leukemia (AML) is a heterogeneous disease whose therapies currently show elevated toxicity and a high rate of relapse. Recently, the burgeoning of new anti-tumor therapeutic strategies aimed at enhancing the immune response has pushed natural killer cells (NKs) into the spotlight. These cells are powerfu...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2018.1539617

    authors: Baragaño Raneros A,López-Larrea C,Suárez-Álvarez B

    更新日期:2018-10-31 00:00:00

  • Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma.

    abstract::We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CT...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1468956

    authors: Bajor DL,Mick R,Riese MJ,Huang AC,Sullivan B,Richman LP,Torigian DA,George SM,Stelekati E,Chen F,Melenhorst JJ,Lacey SF,Xu X,Wherry EJ,Gangadhar TC,Amaravadi RK,Schuchter LM,Vonderheide RH

    更新日期:2018-08-20 00:00:00

  • Breaking the tolerance for tumor: Targeting negative regulators of TLR signaling.

    abstract::Tumors arise and progress in immunocompetent hosts presumably by activating tolerance mechanisms critical for normal homeostasis. Host immune cells can mount anti-tumor responses by activation of Toll-like receptors (TLRs). However, emerging data suggests that molecules that negatively regulate TLRs are exploited by t...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.18434

    authors: Standiford TJ,Keshamouni VG

    更新日期:2012-05-01 00:00:00

  • Tumor evasion of humoral immunity mediated by proteolytic impairment of antibody triggered immune effector function.

    abstract::Immune suppression is recognized as a hallmark of cancer and this notion is largely based on studies on cellular immunity. Our recent studies have demonstrated a potential new mechanism of cancer suppression of immunity by impairment of antibody effector function mediated by proteolytic enzymes in the tumor microenvir...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1122861

    authors: Zhang N,Jordan RE,An Z

    更新日期:2015-12-29 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

  • MDR1 in immunity: friend or foe?

    abstract::MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2018.1499388

    authors: Bossennec M,Di Roio A,Caux C,Ménétrier-Caux C

    更新日期:2018-09-06 00:00:00

  • Standard radiotherapy but not chemotherapy impairs systemic immunity in non-small cell lung cancer.

    abstract::Introduction: Advanced non-small cell lung cancer (NSCLC) is traditionally treated with platinum-based chemotherapy and radiotherapy. Since immunotherapy holds promise for treating advanced NSCLC, we assessed the systemic effects of the traditional therapies for NSCLC on immune cell composition and function. Methods: ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1255393

    authors: Talebian Yazdi M,Schinkelshoek MS,Loof NM,Taube C,Hiemstra PS,Welters MJ,van der Burg SH

    更新日期:2016-11-08 00:00:00

  • Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin.

    abstract::Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of intratumoral injection of recombinant granulysin using in vivo models of breast cancer and mult...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1641392

    authors: Ibáñez-Pérez R,Guerrero-Ochoa P,Al-Wasaby S,Navarro R,Tapia-Galisteo A,De Miguel D,Gonzalo O,Conde B,Martínez-Lostao L,Hurtado-Guerrero R,Sanz L,Anel A

    更新日期:2019-07-22 00:00:00

  • Tbet and IL-36γ cooperate in therapeutic DC-mediated promotion of ectopic lymphoid organogenesis in the tumor microenvironment.

    abstract::We have previously reported that direct injection of dendritic cells (DC) engineered to express the Type-1 transactivator Tbet (i.e., DC.Tbet) into murine tumors results in antitumor efficacy in association with the development of structures resembling tertiary lymphoid organs (TLO) in the tumor microenvironment (TME)...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1322238

    authors: Weinstein AM,Chen L,Brzana EA,Patil PR,Taylor JL,Fabian KL,Wallace CT,Jones SD,Watkins SC,Lu B,Stroncek DF,Denning TL,Fu YX,Cohen PA,Storkus WJ

    更新日期:2017-04-28 00:00:00

  • Blockade of the PD-1 pathway enhances the efficacy of adoptive cell therapy against cancer.

    abstract::The blockade of the PD-1 pathway can increase the production of interferon γ by tumor-specific T cells located within or in the proximity of the malignant lesion, thereby increasing the chemokine-dependent trafficking of immune effector cells. This can boost the efficacy of adoptive T-cell therapy to achieve superior ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.22691

    authors: Peng W,Lizée G,Hwu P

    更新日期:2013-02-01 00:00:00

  • Sepsis inhibits tumor growth in mice with cancer through Toll-like receptor 4-associated enhanced Natural Killer cell activity.

    abstract::Sepsis-induced immune dysfunctions are likely to impact on malignant tumor growth. Sequential sepsis-then-cancer models of tumor transplantation in mice recovering from sepsis have shown that the post-septic immunosuppressive environment was able to promote tumor growth. We herein addressed the impact of sepsis on pre...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1641391

    authors: Vigneron C,Mirouse A,Merdji H,Rousseau C,Cousin C,Alby-Laurent F,Mira JP,Chiche JD,Llitjos JF,Pène F

    更新日期:2019-07-19 00:00:00

  • 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 A2...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1368605

    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

    更新日期:2017-09-21 00:00:00

  • A novel strategy for modulation of MDSC to enhance cancer immunotherapy.

    abstract::Myeloid derived suppressor cells (MDSC) suppress anti-tumor immune responses. Our recent publication provides evidence that SHIP-1 plays a prominent role in pancreatic tumor development by regulating MDSC. Therefore, SHIP-1 may be a potential therapeutic target for the treatment of MDSC-related hematological malignanc...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.20201

    authors: Ghansah T

    更新日期:2012-09-01 00:00:00

  • Notch and TGFβ: Functional partners facilitating tumor progression.

    abstract::Cell signals integral to the tumor microenvironment influence cancer progression. Tumor-associated myeloid cells secrete pro-tumorigenic agents including, but not limited to, the potent cytokine transforming growth factor β (TGFβ). We have discovered a network of extrinsic signals including delta-like 4 (Dll4), Notch ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.29029

    authors: Ohnuki H,Tosato G

    更新日期:2014-05-23 00:00:00

  • Current Clinical Evidence and Potential Solutions to Increase Benefit of CAR T-Cell Therapy for Patients with Solid Tumors.

    abstract::Immunotherapy by chimeric antigen receptor (CAR)-modified T-cells has shown unprecedented clinical efficacy for hematological malignancies. Recently two CAR T-cell based therapeutics, Kymriah (Tisagenlecleucel) and Yescarta (Axicabtagene ciloleucel) were approved by the US Food and Drug Administration and by the Europ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2020.1777064

    authors: Alcantara M,Du Rusquec P,Romano E

    更新日期:2020-06-10 00:00:00