The Critical, Clinical Role of Interferon-Beta in Regulating Cancer Stem Cell Properties in Triple-Negative Breast Cancer

Doherty, Mary R.; Jackson, Mark W.

doi:10.1089/dna.2018.4247

Cited by 12 publications

(12 citation statements)

References 17 publications

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“…In vitro exposure of neuT + mammospheres and cell lines to anti-IFN-I antibodies resulted in increased frequency of ALDH + cells, suggesting that IFN-I control stemness in tumor cells. This finding is consistent with in vitro data on human CSC [ 30 ] and with recent results showing a critical role for a mir-199-LCOR-IFN-I axis in breast CSC biology in mouse models [ 31 ].…”

Section: Type I Interferons and Cancersupporting

confidence: 92%

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

Gessani

Belardelli

2021

Cancers

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Type I interferons (IFN-I) are antiviral cytokines endowed with multiple biological actions, including antitumor activity. Studies in mouse models and cancer patients support the concept that endogenous IFN-I play important roles in the control of tumor development and growth as well as in response to several chemotherapy/radiotherapy treatments. While IFN-I signatures in the tumor microenvironment are often considered as biomarkers for a good prognostic response to antitumor therapies, prolonged IFN-I signaling can lead to immune dysfunction, thereby promoting pathogen or tumor persistence, thus revealing the “Janus face” of these cytokines in cancer control, likely depending on timing, tissue microenvironment and cumulative levels of IFN-I signals. Likewise, IFN-I exhibit different and even opposite effects on obesity, a pathologic condition linked to cancer development and growth. As an example, evidence obtained in mouse models shows that localized expression of IFN-I in the adipose tissue results in inhibition of diet–induced obesity, while hyper-production of these cytokines by specialized cells such as plasmacytoid dendritic cells in the same tissue, can induce systemic inflammatory responses leading to obesity. Further studies in mouse models and humans should reveal the mechanisms by which IFN-I can regulate both tumor growth and obesity and to understand the role of factors such as genetic background, diet and microbioma in shaping the production and action of these cytokines under physiological and pathological conditions.

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Section: Type I Interferons and Cancersupporting

confidence: 92%

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

Gessani

Belardelli

2021

Cancers

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“…Besides being consistent with experimental data showing a close relationship between IFN-I and CSC [39,41], these results corroborate clinical data showing that an impaired IFN-I signaling correlates with a worse clinical outcome and a lower therapy responsiveness in cancer [6,12,39]. Accumulating evidence indicates a specific role for IFN-β, even when administered at a low dose, in counteracting CSC stemness in breast cancer, not only through immunomodulating mechanisms, but also by transcriptionally controlling CSC differentiation [40,42]. Further steps in IFN-I research need to conclusively dissect the role of endogenous and exogenous IFN-I on the biology of CSC in different clinical settings.…”

Section: Ifn-i In Antitumor Therapies Targeting Cancer Stem Cells (Csc)supporting

confidence: 87%

Type I Interferons and Cancer: An Evolving Story Demanding Novel Clinical Applications

Aricò

Castiello

Capone

et al. 2019

Cancers

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The first report on the antitumor effects of interferon α/β (IFN-I) in mice was published 50 years ago. IFN-α were the first immunotherapeutic drugs approved by the FDA for clinical use in cancer. However, their clinical use occurred at a time when most of their mechanisms of action were still unknown. These cytokines were being used as either conventional cytostatic drugs or non-specific biological response modifiers. Specific biological activities subsequently ascribed to IFN-I were poorly considered for their clinical use. Notably, a lot of the data in humans and mice underlines the importance of endogenous IFN-I, produced by both immune and tumor cells, in the control of tumor growth and in the response to antitumor therapies. While many oncologists consider IFN-I as “dead drugs”, recent studies reveal new mechanisms of action with potential implications in cancer control and immunotherapy response or resistance, suggesting novel rationales for their usage in target and personalized anti-cancer treatments. In this Perspectives Article, we focus on the following aspects: (1) the added value of IFN-I for enhancing the antitumor impact of standard anticancer treatments (chemotherapy and radiotherapy) and new therapeutic approaches, such as check point inhibitors and epigenetic drugs; (2) the role of IFN-I in the control of cancer stem cells growth and its possible implications for the development of novel antitumor therapies; and (3) the role of IFN-I in the development of cancer vaccines and the intriguing therapeutic possibilities offered by in situ delivery of ex vivo IFN-stimulated dendritic cells.

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“…The relationship between high folic acid intake and reduced natural killer cell cytotoxicity was also confirmed in murine studies and was, at least partially, attributed to reduced interleukin (IL)-10 production with excess folic acid [71]. Our observation that folic acid withdrawal might reactivate interferon signaling in mesenchymal TNBC cells is of particular interest from a clinical perspective since such reactivation has been considered a promising therapeutic target [59,72,73]. TNBC cells characterized by active INF / STAT signaling are viewed as 'hot' tumors that show prognostic benefits over TNBC subtypes with immune-repressed traits ('cold' tumors) [72,74,75].…”

Section: Discussionmentioning

confidence: 52%