Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells.

Abstract:

:Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that interferon alpha (IFNα)-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFNα alone. Interestingly, IFNα-primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFNα and IFNβ (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting inducible NO synthase (iNOS) expression in IFNγ and TNFα-stimulated MSCs. Notably, only NO production was inhibited by IFNα; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFNα promoted the switch from signal transducer and activator of transcription 1 (Stat1) homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFNα suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy.

journal_name

Oncogene

journal_title

Oncogene

authors

Shou P,Chen Q,Jiang J,Xu C,Zhang J,Zheng C,Jiang M,Velletri T,Cao W,Huang Y,Yang Q,Han X,Zhang L,Wei L,Rabson AB,Chin YE,Wang Y,Shi Y

doi

10.1038/onc.2016.128

subject

Has Abstract

pub_date

2016-11-17 00:00:00

pages

5953-5962

issue

46

eissn

0950-9232

issn

1476-5594

pii

onc2016128

journal_volume

35

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis.

    abstract::Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201225

    authors: Keeling SL,Gad JM,Cooper HM

    更新日期:1997-08-07 00:00:00

  • Interaction of ETS-1 and ERGB/FLI-1 proteins with DNA is modulated by spacing between multiple binding sites as well as phosphorylation.

    abstract::ETS is a family of transcription factors that contain a highly conserved ETS DNA binding domain. Various members of the ETS family are expressed in cells of hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR contain...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Hodge DR,Robinson L,Watson D,Lautenberger J,Zhang XK,Venanzoni M,Seth A

    更新日期:1996-01-04 00:00:00

  • CD44 cleavage induced by a membrane-associated metalloprotease plays a critical role in tumor cell migration.

    abstract::CD44 is a cell surface receptor for hyaluronate, a component of the extracellular matrix (ECM). Although CD44 has been implicated in tumor invasion and metastasis, the molecular mechanisms remain to be elucidated. Here we find that CD44 expressed in cancer cells is cleaved at the membrane-proximal region of the ectodo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202447

    authors: Okamoto I,Kawano Y,Tsuiki H,Sasaki J,Nakao M,Matsumoto M,Suga M,Ando M,Nakajima M,Saya H

    更新日期:1999-02-18 00:00:00

  • Isolation of a distinct class of gain-of-function SHP-2 mutants with oncogenic RAS-like transforming activity from solid tumors.

    abstract::SHP-2 protein tyrosine phosphatase plays an important role in activation of the RAS-dependent signaling. Gain-of-function mutations in the PTPN11 gene, which encodes SHP-2, have been found in the leukemia-prone developmental disorder Noonan syndrome as well as sporadic childhood leukemias, indicating that SHP-2 is a b...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1211019

    authors: Miyamoto D,Miyamoto M,Takahashi A,Yomogita Y,Higashi H,Kondo S,Hatakeyama M

    更新日期:2008-06-05 00:00:00

  • CXCR7/CXCR4 heterodimer-induced histone demethylation: a new mechanism of colorectal tumorigenesis.

    abstract::Both chemokine receptors (CXCRs) 7 and 4 can facilitate immune cell migration and mediate a vast array of physiological and pathological events. Herein we report, in both human and animal studies, that these two CXCRs can form heterodimers in vivo and promote colorectal tumorigenesis through histone demethylation. Com...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0519-2

    authors: Song ZY,Wang F,Cui SX,Gao ZH,Qu XJ

    更新日期:2019-02-01 00:00:00

  • Age-dependent and tissue-specific changes of DNA methylation within and around the c-fos gene in mice.

    abstract::The degree of DNA methylation in the c-fos gene and its vicinity in liver, brain and spleen of mice of different ages was examined using methylation-sensitive restriction endonucleases. The gene had an invariable unmethylated domain from 1.8kb upstream of the cap site to the first intron. The domain was flanked on bot...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Uehara Y,Ono T,Kurishita A,Kokuryu H,Okada S

    更新日期:1989-08-01 00:00:00

  • Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway.

    abstract::Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and f...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.174

    authors: Park JH,Lee JY,Shin DH,Jang KS,Kim HJ,Kong G

    更新日期:2011-11-10 00:00:00

  • Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors.

    abstract::Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accum...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.519

    authors: Obata Y,Horikawa K,Takahashi T,Akieda Y,Tsujimoto M,Fletcher JA,Esumi H,Nishida T,Abe R

    更新日期:2017-06-29 00:00:00

  • Mode of action of trabectedin in myxoid liposarcomas.

    abstract::To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respect...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.462

    authors: Di Giandomenico S,Frapolli R,Bello E,Uboldi S,Licandro SA,Marchini S,Beltrame L,Brich S,Mauro V,Tamborini E,Pilotti S,Casali PG,Grosso F,Sanfilippo R,Gronchi A,Mantovani R,Gatta R,Galmarini CM,Sousa-Faro JM,D'Incalc

    更新日期:2014-10-30 00:00:00

  • Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer.

    abstract::Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 (proline, glutamic acid and leucine rich protein 1) is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer pat...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.332

    authors: Roy SS,Gonugunta VK,Bandyopadhyay A,Rao MK,Goodall GJ,Sun LZ,Tekmal RR,Vadlamudi RK

    更新日期:2014-07-10 00:00:00

  • Impact of G₂ checkpoint defect on centromeric instability.

    abstract::Centromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.508

    authors: Deng W,Tsao SW,Mak GW,Tsang CM,Ching YP,Guan XY,Huen MS,Cheung AL

    更新日期:2011-03-17 00:00:00

  • Predominant requirement of Bax for apoptosis in HCT116 cells is determined by Mcl-1's inhibitory effect on Bak.

    abstract::The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.497

    authors: Wang C,Youle RJ

    更新日期:2012-06-28 00:00:00

  • RARgamma acts as a tumor suppressor in mouse keratinocytes.

    abstract::All-trans retinoic acid (RA), the principle biologically active form of vitamin A, is essential for many developmental process as well as homeostasis in the adult. Many lines of evidence also suggest that RA, acting through the RA receptors (RARs), can also suppress growth of tumors of diverse origin. To assess direct...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207682

    authors: Chen CF,Goyette P,Lohnes D

    更新日期:2004-07-08 00:00:00

  • Bruton's tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma.

    abstract::Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton's tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma ce...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0397-7

    authors: Li T,Deng Y,Shi Y,Tian R,Chen Y,Zou L,Kazi JU,Rönnstrand L,Feng B,Chan SO,Chan WY,Sun J,Zhao H

    更新日期:2018-11-01 00:00:00

  • THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies.

    abstract::Promyelocytic leukemia (PML) nuclear bodies (PML NBs) are discrete subnuclear domains organized by the promyelocytic leukemia protein PML, a tumor suppressor essential for multiple apoptotic pathways. We have recently described a novel family of cellular factors, the THAP proteins, characterized by the presence at the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206271

    authors: Roussigne M,Cayrol C,Clouaire T,Amalric F,Girard JP

    更新日期:2003-04-24 00:00:00

  • Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells.

    abstract::Nerve growth factor induces differentiation and survival of rat PC12 pheochromocytoma cells. The activation of the erk cascade has been implicated in transducing the multitude of signals induced by NGF. In order to explore the role of this signaling cascade in NGF mediated survival, differentiation and proliferation, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202524

    authors: Klesse LJ,Meyers KA,Marshall CJ,Parada LF

    更新日期:1999-03-25 00:00:00

  • The adenovirus E1A 289R and 243R proteins inhibit the phosphorylation of p300.

    abstract::A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Banerjee AC,Recupero AJ,Mal A,Piotrkowski AM,Wang DM,Harter ML

    更新日期:1994-06-01 00:00:00

  • c-myc and p53 gene expression in the differentiation of temperature-sensitive mutants of teratocarcinoma F9 cells.

    abstract::We have previously reported the isolation of several temperature-sensitive (ts) mutants of F9 cells. Further investigations showed that some mutants were induced to differentiate at non-permissive temperature of cell growth, accompanied by changes in the expression of various genes, whereas others were not. During the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Kosaka M,Iwai SA,Nishina Y,Sumi T,Nishimune Y

    更新日期:1992-12-01 00:00:00

  • BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb.

    abstract::The carboxyl terminus of c-Myb contains a negative regulatory domain that is absent in the v-Myb oncoprotein, but conserved among all the known Myb proteins of animals. This domain inhibits transcriptional activation by c-Myb in animal cells, but not in budding yeast, suggesting that additional protein(s) present in a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204048

    authors: Ladendorff NE,Wu S,Lipsick JS

    更新日期:2001-01-04 00:00:00

  • Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016.

    abstract::The expression of the NH2 terminally truncated ErbB2 receptor (p95ErbB2) in breast cancer correlates with metastatic disease progression compared with the expression of full-length p185ErbB2. We now show that heregulin (HRG), but not EGF, stimulates p95ErbB2 phosphorylation in BT474 breast cancer cells. Furthermore, p...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207166

    authors: Xia W,Liu LH,Ho P,Spector NL

    更新日期:2004-01-22 00:00:00

  • Control of MAPK signalling: from complexity to what really matters.

    abstract::Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208817

    authors: Hornberg JJ,Binder B,Bruggeman FJ,Schoeberl B,Heinrich R,Westerhoff HV

    更新日期:2005-08-25 00:00:00

  • High prognostic significance of Mdm2/p53 co-overexpression in soft tissue sarcomas of the extremities.

    abstract::Soft tissue sarcomas are a heterogeneous group of neoplasms with various histological subtypes. Up to now, no individual causal molecular markers for prognosis and therapeutic success have been identified. A tumorigenic connection between the oncogene product Mdm2 and tumor suppressor p53 is generally accepted, but th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201646

    authors: Würl P,Meye A,Schmidt H,Lautenschläger C,Kalthoff H,Rath FW,Taubert H

    更新日期:1998-03-05 00:00:00

  • Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol.

    abstract::A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf P...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Troppmair J,Bruder JT,App H,Cai H,Liptak L,Szeberényi J,Cooper GM,Rapp UR

    更新日期:1992-09-01 00:00:00

  • p53- and p21-dependent premature APC/C-Cdh1 activation in G2 is part of the long-term response to genotoxic stress.

    abstract::The long-term cellular response to DNA damage is controlled by the tumor suppressor p53. It results in cell-cycle arrest followed by DNA repair and, depending on the degree of damage inflicted, premature senescence or apoptotic cell death. Here we show that in normal diploid fibroblasts the ubiquitin ligase anaphase-p...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.99

    authors: Wiebusch L,Hagemeier C

    更新日期:2010-06-17 00:00:00

  • The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor.

    abstract::Topors was identified recently as a human protein that binds to topoisomerase I and p53. Topors contains a highly conserved RING domain and localizes in promyelocytic leukemia nuclear bodies. Relatively little is known regarding topors expression patterns or function. We now demonstrate that topors mRNA and protein ar...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207700

    authors: Saleem A,Dutta J,Malegaonkar D,Rasheed F,Rasheed Z,Rajendra R,Marshall H,Luo M,Li H,Rubin EH

    更新日期:2004-07-08 00:00:00

  • Induction of hepatocyte proliferation and liver hyperplasia by the targeted expression of cyclin E and skp2.

    abstract::Cells in culture become competent to replicate in the absence of growth factor after progressing beyond the late G1 restriction point, suggesting that a set of genes expressed during G1 phase is sufficient to trigger completion of the cell cycle. However, this has not been demonstrated in an in vivo system. In this st...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204248

    authors: Nelsen CJ,Hansen LK,Rickheim DG,Chen C,Stanley MW,Krek W,Albrecht JH

    更新日期:2001-04-05 00:00:00

  • The pleiotropic effects of TNFα in breast cancer subtypes is regulated by TNFAIP3/A20.

    abstract::TNFα is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNFα exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0472-0

    authors: Lee E,Ouzounova M,Piranlioglu R,Ma MT,Guzel M,Marasco D,Chadli A,Gestwicki JE,Cowell JK,Wicha MS,Hassan KA,Korkaya H

    更新日期:2019-01-01 00:00:00

  • Delineation of the domains required for physical and functional interaction of p14ARF with human topoisomerase I.

    abstract::We recently reported an interaction between the p14(ARF) protein and human topoisomerase I (Topo I) resulting in the stimulation of the relaxation activity of Topo I. Our data showed that the complex between the two proteins was located within the nucleolus. In the present work, we have investigated the regions of p14...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206214

    authors: Ayrault O,Karayan L,Riou JF,Larsen CJ,Séité P

    更新日期:2003-04-03 00:00:00

  • Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation.

    abstract::As tumors grow and invade beyond their homeostatic limits, the tumor cells are subjected to insufficient nutrient and oxygen supplies because of excessive demand for nutrition and oxygen, and insufficient vascularization. We therefore hypothesized that tolerance to nutrient deprivation as well as angiogenesis may be c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205737

    authors: Kato K,Ogura T,Kishimoto A,Minegishi Y,Nakajima N,Miyazaki M,Esumi H

    更新日期:2002-09-05 00:00:00

  • Aberrant activation of ALK kinase by a novel truncated form ALK protein in neuroblastoma.

    abstract::Anaplastic lymphoma kinase (ALK) was originally identified from a rare subtype of non-Hodgkin's lymphomas carrying t(2;5)(p23;q35) translocation, where ALK was constitutively activated as a result of a fusion with nucleophosmin (NPM). Aberrant ALK fusion proteins were also generated in inflammatory fibrosarcoma and a ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.616

    authors: Okubo J,Takita J,Chen Y,Oki K,Nishimura R,Kato M,Sanada M,Hiwatari M,Hayashi Y,Igarashi T,Ogawa S

    更新日期:2012-11-01 00:00:00