Increased protein nitrosylation in head and neck squamous cell carcinogenesis

Bentz, Brandon G.; Haines, G. Kenneth; Radosevich, James A.

doi:10.1002/(sici)1097-0347(200001)22:1<64::aid-hed10>3.0.co;2-j

Cited by 54 publications

(29 citation statements)

References 21 publications

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“…Peroxynitrites produced during inflammatory conditions were directly implicated in the promotion of tumor progression via modification and inactivation of different proteins. An association of high peroxynitrite levels with tumor progression was documented for pancreatic cancer, malignant gliomas, head and neck cancer, breast cancer, melanoma, and mesothelioma (17)(18)(19)(20)(21).…”

Section: A Model Of Mdsc-inducible T-cell Tolerancementioning

confidence: 99%

Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells

2008

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T-cell nonresponsiveness is a critical factor in immune escape and myeloid-derived suppressor cells play a major role in organizing this phenomenon. Recent findings indicate that myeloid-derived suppressor cells can induce antigen-specific CD8 + T-cell tolerance through a posttranslation mechanism which involves modification (nitration) of CD8 and the T-cell receptor itself on the T-cell surface. Elucidation of this mechanism of T-cell tolerance offers new opportunities for therapeutic corrections of immune escape in cancer. [Cancer Res 2008;68(8):2561-63] Myeloid-Derived Suppressor Cells and Tumor EscapeDefective T-cell function represents one of the major mechanisms of tumor escape and one of the critical factors limiting the success of cancer vaccines. Tumor-induced T-cell abnormalities include antigen-specific nonresponsiveness (anergy/tolerance), deletion of T cells by apoptosis, and nonspecific suppression of T-cell function.In both animal models of cancer and in the clinical setting, unresponsiveness of T cells to tumor-specific antigens has been shown to be an early event in tumor progression. Studies have established that in tumor-bearing mice, a group of bone marrow-derived cells recently termed myeloid-derived suppressor cells (MDSC) are directly involved in the suppression of immune responses in cancer. These cells express both myeloid lineage differentiation antigen Gr-1 (Ly6G and Ly6C) and a M integrin CD11b, and in control mice represent f20% to 30% of normal bone marrow cells, 2% to 4% of all nucleated splenocytes, and are practically absent in lymph nodes. Inoculation with tumor cells or the development of spontaneous tumors results in a marked systemic expansion of these cells (1, 2). The number of MDSCs in spleens increase by 5-to 20-fold depending on the tumor model. These cells are also easily detected in lymph nodes or tumor sites. Similar expansion, albeit to a lesser degree, is observed in patients with cancer. In humans, MDSC are generally defined as CD14 À CD11b+ cells, or more narrowly, as the cells that express the common myeloid marker CD33, but lack the expression of markers of mature myeloid and lymphoid cells (1, 2).Numerous studies have established the potent immunosuppressive potential of MDSC. MDSCs may exert an immunosuppressive effect in both an antigen-specific and nonspecific manner depending on their localization and the specific characteristics of the tumor. Several different factors are implicated in MDSC-mediated immune suppression. They include arginase, reactive oxygen and nitrogen species, as well as inhibitory surface molecules. It seems that in the tumor site, the immunosuppressive activity of MDSC is antigen-nonspecific and is primarily mediated by the production of nitric oxide (NO) in combination with a high arginase activity. NO could inhibit T cells via a variety of different mechanisms involving the blockade of phosphorylation and activation of Janus kinase 3, STAT5 transcription factor, inhibition of MHC class II gene expression, and induction o...

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Section: A Model Of Mdsc-inducible T-cell Tolerancementioning

confidence: 99%

Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells

2008

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“…Peroxynitrite induces the nitration and nitrosylation of the amino acids cysteine, methionine, tryptophan and tyrosine. Increased levels of peroxynitrite are associated with tumour progression in many types of cancer [49][50][51][52][53][54], which has been linked with T-cell unresponsiveness. …”

Section: Peroxynitritementioning

confidence: 99%

The emerging role of myeloid-derived suppressor cells in lung diseases

et al. 2016

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Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. @ERSpublications Myeloid-derived suppressor cells are involved in various lung diseases and represent promising therapeutic targets

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“…In addition, PNT can react directly with cysteine, methionine, and tryptophan (11). A substantial number of studies have demonstrated high levels of nitrotyrosine (NT) in different types of cancer, including pancreatic cancer (12), malignant gliomas (13), head and neck cancer (14), mesothelioma (15), colon carcinoma (16), invasive breast carcinomas (17), melanoma (18,19), and lung cancer (20). In patients with breast cancer, high tumor NT levels were associated with reduced disease-free and overall survival.…”

Section: Introductionmentioning

confidence: 99%

Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice

et al. 2011

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Cancer immunotherapeutic approaches induce tumor-specific immune responses, in particular CTL responses, in many patients treated. However, such approaches are clinically beneficial to only a few patients. We set out to investigate one possible explanation for the failure of CTLs to eliminate tumors, specifically, the concept that this failure is not dependent on inhibition of T cell function. In a previous study, we found that in mice, myeloidderived suppressor cells (MDSCs) are a source of the free radical peroxynitrite (PNT). Here, we show that pretreatment of mouse and human tumor cells with PNT or with MDSCs inhibits binding of processed peptides to tumor cell-associated MHC, and as a result, tumor cells become resistant to antigen-specific CTLs. This effect was abrogated in MDSCs treated with a PNT inhibitor. In a mouse model of tumor-associated inflammation in which the antitumor effects of antigen-specific CTLs are eradicated by expression of IL-1β in the tumor cells, we determined that therapeutic failure was not caused by more profound suppression of CTLs by IL-1β-expressing tumors than tumors not expressing this proinflammatory cytokine. Rather, therapeutic failure was a result of the presence of PNT. Clinical relevance for these data was suggested by the observation that myeloid cells were the predominant source of PNT in human lung, pancreatic, and breast cancer samples. Our data therefore suggest what we believe to be a novel mechanism of MDSC-mediated tumor cell resistance to CTLs.

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Increased protein nitrosylation in head and neck squamous cell carcinogenesis

Cited by 54 publications

References 21 publications

Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells

Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells

The emerging role of myeloid-derived suppressor cells in lung diseases

Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice

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