Interferons, immunity and cancer immunoediting

Washington University School of Medicine, Department of Pathology and Immunology, Box 8118, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Nature reviews. Immunology (Impact Factor: 33.84). 12/2006; 6(11):836-48. DOI: 10.1038/nri1961
Source: PubMed

ABSTRACT A clear picture of the dynamic relationship between the host immune system and cancer is emerging as the cells and molecules that participate in naturally occurring antitumour immune responses are being identified. The interferons (IFNs) - that is, the type I IFNs (IFNalpha and IFNbeta) and type II IFN (IFNgamma) - have emerged as central coordinators of tumour-immune-system interactions. Indeed, the decade-old finding that IFNgamma has a pivotal role in promoting antitumour responses became the focus for a renewed interest in the largely abandoned concept of cancer immunosurveillance. More recently, type I IFNs have been found to have distinct functions in this process. In this Review, we discuss the roles of the IFNs, not only in cancer immunosurveillance but also in the broader process of cancer immunoediting.

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    • "Of interest, immune response is intimately related to both diseases [5] [6] [7]. In fact, based on an early colorectal cancer (CRC) transcriptome dataset [8], our previous study [9] found immunosuppression and immune cell infiltration even within normal-appearing cells in CRC patients. "
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    BioMed Research International 02/2015; · 2.71 Impact Factor
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    • "The importance of IFN signaling in human cancer is still a debated topic, but most commonly, activation of a type I IFN signature is thought to be tumor suppressive (Chan et al., 2012; Yu et al., 2009). In fact, type I IFN is an approved treatment for many diverse cancer types (Dunn et al., 2006). Our work provides evidence for the direct involvement of IFN-b, STAT1, and a downstream ISG, ISG15, in promoting tumorigenicity. "
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    ABSTRACT: The ARF and p53 tumor suppressors are thought to act in a linear pathway to prevent cellular transformation in response to various oncogenic signals. Here, we show that loss of p53 leads to an increase in ARF protein levels, which function to limit the proliferation and tumorigenicity of p53-deficient cells by inhibiting an IFN-β-STAT1-ISG15 signaling axis. Human triple-negative breast cancer (TNBC) tumor samples with coinactivation of p53 and ARF exhibit high expression of both STAT1 and ISG15, and TNBC cell lines are sensitive to STAT1 depletion. We propose that loss of p53 function and subsequent ARF induction creates a selective pressure to inactivate ARF and propose that tumors harboring coinactivation of ARF and p53 would benefit from therapies targeted against STAT1 and ISG15 activation.
    Cell Reports 04/2014; 7(2). DOI:10.1016/j.celrep.2014.03.026 · 7.21 Impact Factor
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    • "Whereas IFN-a/b primarily exerts its effects on macrophages, DCs, and NK cells by facilitating their activation and maturation and by enhancing their capacity to induce adaptive immune responses (Dunn et al. 2006), IFN-c directly affects the tumor via inhibition of tumor cell proliferation, apoptosis induction, inhibition of angiogenesis, and an overall enhancement of tumor immunogenicity (Dunn et al. 2006; Lugade et al. 2008; Reits et al. 2006). Additionally, IFN-c contributes to the stimulation of an antitumor immune response since it is essentially involved in T H 1/T C 1 cell responses and exerts similar effects as IFN-a/b in terms of innate immune cell activation and DC-mediated antigen cross-presentation (Dunn et al. 2006). This interferon cascade of innate and adaptive immune responses has only been described in case of ablative but not conventional, fractionated radiotherapy (Lee et al. 2009), and the question that needs to be addressed is why. "
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    ABSTRACT: Based on its potent capacity to induce tumor cell death and to abrogate clonogenic survival, radiotherapy is a key part of multimodal cancer treatment approaches. Numerous clinical trials have documented the clear correlation between improved local control and increased overall survival. However, despite all progress, the efficacy of radiation-based treatment approaches is still limited by different technological, biological, and clinical constraints. In principle, the following major issues can be distinguished: (1) The intrinsic radiation resistance of several tumors is higher than that of the surrounding normal tissue, (2) the true patho-anatomical borders of tumors or areas at risk are not perfectly identifiable, (3) the treatment volume cannot be adjusted properly during a given treatment series, and (4) the individual heterogeneity in terms of tumor and normal tissue responses toward irradiation is immense. At present, research efforts in radiation oncology follow three major tracks, in order to address these limitations: (1) implementation of molecularly targeted agents and 'omics'-based screening and stratification procedures, (2) improvement of treatment planning, imaging, and accuracy of dose application, and (3) clinical implementation of other types of radiation, including protons and heavy ions. Several of these strategies have already revealed promising improvements with regard to clinical outcome. Nevertheless, many open questions remain with individualization of treatment approaches being a key problem. In the present review, the current status of radiation-based cancer treatment with particular focus on novel aspects and developments that will influence the field of radiation oncology in the near future is summarized and discussed.
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