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: 34.99). 12/2006; 6(11):836-48. DOI: 10.1038/nri1961
Source: PubMed


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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    • "Once they have migrated to the tumor microenvironment , immune cells can mediate cytotoxic effects, in part through the release of various interferons. Type 1 interferons (IFNα and IFNβ) play an important role in the immune response to viral infection, but are also critical to anti-tumor immune responses (Dunn et al., 2006). Mouse melanoma models have suggested increases in IFNα after single-dose of 15 Gy (Lim et al., 2014). "
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    ABSTRACT: Radiation therapy plays an important role in the treatment of the majority of cancers, and is commonly used to treat both localized and metastatic disease. Immunotherapy has recently been firmly integrated into the treatment of metastatic melanoma, and holds significant promise in treating a variety of other cancers. Although large field radiation has historically been appreciated for its immunosuppressive ability, targeted radiation can induce substantial changes in the tumor microenvironment beyond cellular cytotoxicity that evoke innate and adaptive immune responses. Previous studies have highlighted radiation-induced changes in proinflammatory cytokines, chemokines, effector, and immunosuppressive T cell subsets, as well as in immune receptors on tumor cells. Some of these changes in localized and systemic immune mediators have been linked to expansion of tumor-reactive T cells, improved clinical responses, and increased overall survival in preclinical and clinical models. Taken together, this evidence suggests that targeted radiation therapy can impact anti-tumor immune responses, and may potentially be combined with immunotherapy for synergistic effect.
    Discovery medicine 03/2015; 19(104):219-28. · 3.63 Impact Factor
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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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    ABSTRACT: Recently, a large clinical study revealed an inverse correlation of individual risk of cancer versus Alzheimer's disease (AD). However, no explanation exists for this anticorrelation at the molecular level; however, inflammation is crucial to the pathogenesis of both diseases, necessitating a need to understand differing signaling usage during inflammatory responses distinct to both diseases. Using a subpathway analysis approach, we identified numerous well-known and previously unknown pathways enriched in datasets from both diseases. Here, we present the quantitative importance of the inflammatory response in the two disease pathologies and summarize signal transduction pathways common to both diseases that are affected by inflammation.
    BioMed Research International 02/2015; 2015(9). DOI:10.1155/2015/205247 · 2.71 Impact Factor
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    • "However, the level of INFγ-production per cell was significantly higher in mice that were treated by a combination of CSF-1R inhibition and CD8 T-cell based immunotherapy (Fig 5). The importance of INFγ in the immune control of tumors is widely described [16] and reduced presence of macrophages in the local tumor environment is likely to empower effector functions of intratumoral T cells. Immune suppressive activity of M2-type macrophages have been thoroughly investigated in mouse and human tumors and mechanisms of dampening T cell effector functions include nitrosylation of TCR, production of immunosuppressive cytokines IL-10 and TGFβ and amino acid deprivation [3], [14], [17]. "
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    ABSTRACT: Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1+ myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNγ production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors.
    PLoS ONE 08/2014; 9(8):e104230. DOI:10.1371/journal.pone.0104230 · 3.23 Impact Factor
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