Impaired interferon signaling is a common immune defect in human cancer

Critchley-Thorne, Rebecca J.; Simons, Diana L.; Yan, Ning; Miyahira, Andrea K.; Dirbas, Frederick M.; Johnson, Denise; Swetter, Susan M.; Carlson, R. W.; Fisher, George A.; Koong, Albert C.; Holmes, Susan; Lee, Peter P.

doi:10.1073/pnas.0901329106

Cited by 223 publications

(204 citation statements)

References 35 publications

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“…The commonly found dysfunction of NK cells in breast cancer patients [120][121][122] is probably the consequence of cytokine dysbalance due to the prevalence of immunosuppressive cytokines such as IL-10 and TGF [123], as well as tumor-produced inhibitory factors [124]. This finding is in concordance with the only previous study published for breast cancer patients [125] and also with several other investigations showing STAT dysregulation in PBL of melanoma and renal cell carcinoma patients [126,127]. Moreover, we showed that breast cancer patients' T and NK cell subsets have lower pSTAT1 level that could be a biomarker of decreased NK cell cytotoxicity and IFN production associated with progression of this disease [120,128,129].…”

Section: Stat Dysfunction Associated With Different Malignanciessupporting

confidence: 83%

STAT Transcription Factors in Tumor Development and Targeted Therapy of Malignancies

Konjević¹,

Radenković²,

Vuletić³

et al. 2013

Oncogene and Cancer - From Bench to Clinic

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Section: Stat Dysfunction Associated With Different Malignanciessupporting

confidence: 83%

STAT Transcription Factors in Tumor Development and Targeted Therapy of Malignancies

Konjević¹,

Radenković²,

Vuletić³

et al. 2013

Oncogene and Cancer - From Bench to Clinic

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“…VSV is a Vesiculovirus of the family Rhabdoviridae with a negative-sense RNA genome (16,17). VSV is a preferred candidate as a platform for oncolytic virus development against a variety of cancers (10,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), primarily due to its very broad tropism infecting a wide variety of animals and different cells, its short replication cycle, and high sensitivity to host interferon-mediated antiviral activity (28)(29)(30)(31)(32)(33)(34)(35). Tumor-selective tropism can be further enhanced by mutating the M protein or engineering the virus to encode beta interferon (IFN-␤).…”

mentioning

confidence: 99%

Vesiculovirus Neutralization by Natural IgM and Complement

Tesfay

Ammayappan

Federspiel

et al. 2014

J Virol

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Because of its very low human seroprevalence, vesicular stomatitis virus (VSV) has promise as a systemic oncolytic agent for human cancer therapy. However, as demonstrated in this report, the VSV infectious titer drops by 4 log units during the first hour of exposure to nonimmune human serum. This neutralization occurs relatively slowly and is mediated by the concerted actions of natural IgM and complement. Maraba virus, whose G protein is about 80% homologous to that of VSV, is relatively resistant to the neutralizing activity of nonimmune human serum. We therefore constructed and rescued a recombinant VSV whose G gene was replaced by the corresponding gene from Maraba virus. Comparison of the parental VSV and VSV with Maraba G substituted revealed nearly identical host range properties and replication kinetics on a panel of tumor cell lines. Moreover, in contrast to the parental VSV, the VSV with Maraba G substituted was resistant to nonimmune human serum. Overall, our data suggest that VSV with Maraba G substituted should be further investigated as a candidate for human systemic oncolytic virotherapy applications. IMPORTANCEOncolytic virotherapy is a promising approach for the treatment of disseminated cancers, but antibody neutralization of circulating oncolytic virus particles remains a formidable barrier. In this work, we developed a pseudotyped vesicular stomatitis virus (VSV) with a glycoprotein of Maraba virus, a closely related but serologically distinct member of the family Rhabdoviridae, which demonstrated greatly diminished susceptibility to both nonimmune and VSV-immune serum neutralization. VSV with Maraba G substituted or lentiviral vectors should therefore be further investigated as candidates for human systemic oncolytic virotherapy and gene therapy applications.

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“…Depending upon the target cell, IFNs can inhibit the progression of the cell cycle or can evoke apoptosis. IFN signaling defects are common in several human cancers (4). In certain cases IFN response is essential for tumor therapy with DNA-damaging agents (5); in other cases the expression of an IFN-related DNA-damage signature correlates with a lack of therapeutic response (6).…”

mentioning

confidence: 99%

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Kalakonda¹,

Nallar²,

Jaber

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Gene-associated with retinoid-interferon induced mortality-19 (GRIM-19) is an interferon-retinoid–regulated growth suppressor that inhibits cell growth by targeting the transcription factor STAT3 for inhibition. In primary human tumors GRIM-19 is suppressed or mutated, leading to constitutive STAT3 activity and indicating the tumor-suppressive function of GRIM-19. To understand the in vivo role of Grim-19 in tumor development, we generated a Grim-19 conditional knockout mouse. We found that deletion of even a single Grim-19 allele is sufficient to augment skin tumorigenesis in mice, thus establishing a critical role for Grim-19 as a tumor suppressor. Tumors that developed in the absence of Grim-19 exhibited mitochondrial respiratory chain dysfunction, elevated glycolysis, and Stat3-responsive gene expression.

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Impaired interferon signaling is a common immune defect in human cancer

Cited by 223 publications

References 35 publications

STAT Transcription Factors in Tumor Development and Targeted Therapy of Malignancies

STAT Transcription Factors in Tumor Development and Targeted Therapy of Malignancies

Vesiculovirus Neutralization by Natural IgM and Complement

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

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