Distinct Roles for IFN Regulatory Factor (IRF)-3 and IRF-7 in the Activation of Antitumor Properties of Human Macrophages

Romieu‐Mourez, Raphaëlle; Solis, Mayra; Nardin, Alessandra; Goubau, Delphine; Baron‐Bodo, Véronique; Lin, Rongtuan; Massie, Bernard; Salcedo, Margarita; Hiscott, John

doi:10.1158/0008-5472.can-06-1279

Cited by 83 publications

(79 citation statements)

References 54 publications

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“…The transcription factors for Noxa and TRAIL are IRF3 and IRF7, respectively (36,37), both of which are regulated by MAVS (38). HVJ-E-induced cell death was suppressed by IRF3 siRNA in DU145 cells and by IRF7 siRNA in PC3 cells (Supplementary Fig.…”

Section: Hvj-e-mediated Trail and Noxa Induction Via The Rig-i/mavs Pmentioning

confidence: 99%

“…PC3, A549, MDA-MB-231, and NSF1227 cells were maintained in Dulbecco's modified Eagle's medium (Nacalai Tesque Inc.), and the DU145, LNCaP, PNT1, and PNT2 cells were maintained in RPMI-1640 medium (Nacalai Tesque Inc.), with 10% FBS (Biowest), 100 U/mL penicillin, and 100 mg/mL streptomycin (penicillin-streptomycin mixed solution; Nacalai Tesque Inc.). The cells were incubated at 37 C in a humidified atmosphere of 95% air and 5% CO 2 . Nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice, ages 6 weeks, were purchased from Japan Clea and were maintained in a temperaturecontrolled, pathogen-free room.…”

Section: Cells and Micementioning

confidence: 99%

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TRAIL and Noxa Are Selectively Upregulated in Prostate Cancer Cells Downstream of the RIG-I/MAVS Signaling Pathway by Nonreplicating Sendai Virus Particles

Matsushima-Miyagi

Hatano

Nomura

et al. 2012

Clinical Cancer Research

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Purpose: The treatment of cancer with oncolytic viruses primarily depends on the selective viral replication in cancer cells. However, a replication-incompetent hemagglutinating virus of Japan (HVJ; Sendai virus) envelope (HVJ-E) suppresses the growth of human cancer cells as effectively as replicationcompetent live HVJ without producing toxic effects in nonmalignant cells. Here, we analyze the molecular mechanism of the oncolytic activity of HVJ-E.Experimental Design: The molecules responsible for HVJ-E-induced cancer cell death were elucidated in prostate cancer cell lines, and the effect of HVJ-E on orthotopic prostate cancers was evaluated in nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice.Results: The liposome-mediated transfer of viral RNA genome fragments from HVJ-E suppressed the viability of prostate cancer cells but not the viability of the noncancerous prostate epithelium. Knockdown experiments using siRNAs showed that the cancer cell-selective killing induced by HVJ-E was mediated by retinoic acid-inducible gene I (RIG-I) and mitochondrial antiviral signaling protein (MAVS). Downstream of the RIG-I/MAVS pathway, both TNF-related apoptosis-inducing ligand (TRAIL) and Noxa were upregulated by HVJ-E in the castration-resistant prostate cancer cell line PC3 but not in the noncancerous prostate epithelial cell line PNT2. TRAIL siRNA but not Noxa siRNA significantly inhibited HVJ-E-induced cell death in PC3 cells. However, Noxa siRNA effectively suppressed HVJ-E-induced cell death in DU145 cells, another castration-resistant prostate cancer cell line, in which Noxa but not TRAIL was upregulated by HVJ-E. Furthermore, the orthotopic prostate cancers were dramatically eradicated in immunodeficient mice injected with HVJ-E.Conclusion: The RIG-I/MAVS signaling pathway represents an attractive target for cancer therapy.

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Section: Hvj-e-mediated Trail and Noxa Induction Via The Rig-i/mavs Pmentioning

confidence: 99%

Section: Cells and Micementioning

confidence: 99%

TRAIL and Noxa Are Selectively Upregulated in Prostate Cancer Cells Downstream of the RIG-I/MAVS Signaling Pathway by Nonreplicating Sendai Virus Particles

Matsushima-Miyagi

Hatano

Nomura

et al. 2012

Clinical Cancer Research

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“…16 Several studies have indicated that the phenotype of macrophages can change in vivo over time 17,18 ; for example, it was reported that macrophages in the earliest stages of cancer resembled classically activated macrophages, yet, with tumor growth, macrophages developed a regulatory phenotype. 19,20 Another example is the observation that macrophages in adipose tissue of nonobese humans have a woundhealing phenotype yet can switch to a proinflammatory phenotype in obese individuals. 21,22 It is not clear whether phenotypic deviation can occur in transfused anti-inflammatory macrophages used to treat various diseases.…”

Section: Cd25mentioning

confidence: 99%

IL-10/TGF-β–Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis

Cao

Wang²,

Zheng³

et al. 2010

Journal of the American Society of Nephrology

238

210

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IL-10/TGF-␤-modified macrophages, a subset of activated macrophages, produce anti-inflammatory cytokines, suggesting that they may protect against inflammation-mediated injury. Here, macrophages modified ex vivo by IL-10/TGF-␤ (IL-10/TGF-␤ ⌴2) significantly attenuated renal inflammation, structural injury, and functional decline in murine adriamycin nephrosis (AN). These cells deactivated effector macrophages and inhibited CD4 ϩ T cell proliferation. IL-10/TGF-␤ ⌴2 expressed high levels of the regulatory co-stimulatory molecule B7-H4, induced regulatory T cells from CD4 cells in vitro,and increased the number of regulatory T cells in lymph nodes draining the kidneys in AN. The phenotype of IL-10/TGF-␤ ⌴2 did not switch to that of effector macrophages in the inflamed kidney, and these cells did not promote fibrosis. Taken together, these data demonstrate that IL-10/TGF-␤-modified macrophages effectively protect against renal injury in AN and may become part of a therapeutic strategy for chronic inflammatory disease.

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“…The role of TAMs in tumor progression has been controversial. Early reports correlated macrophage infiltration with tumor suppression (11,12). However, other studies suggested that elevated TAM numbers correlate with poor clinical outcome in many types of human cancers (7,9,10).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation

Imtiyaz¹,

Williams²,

Hickey³

et al. 2010

J. Clin. Invest.

402

406

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Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1α and HIF-2α, and overexpression of HIF-2α in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2α during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1α versus HIF-2α must be elucidated. We demonstrate here that mice lacking HIF-2α in myeloid cells (Hif2a Δ/Δ mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2α directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2a Δ/Δ mice displayed reduced TAM infiltration in independent murine hepatocellular and colitisassociated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2α modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2α as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer.

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Distinct Roles for IFN Regulatory Factor (IRF)-3 and IRF-7 in the Activation of Antitumor Properties of Human Macrophages

Cited by 83 publications

References 54 publications

TRAIL and Noxa Are Selectively Upregulated in Prostate Cancer Cells Downstream of the RIG-I/MAVS Signaling Pathway by Nonreplicating Sendai Virus Particles

TRAIL and Noxa Are Selectively Upregulated in Prostate Cancer Cells Downstream of the RIG-I/MAVS Signaling Pathway by Nonreplicating Sendai Virus Particles

IL-10/TGF-β–Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis

Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation

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