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Type I Interferons: A Double-Edged Sword of Immune Regulation and...
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Type I Interferons: A Double-Edged Sword of Immune Regulation and Cancer Progression

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 17555

Special Issue Editors

Dr. Alessandra Soriani

E-Mail Website
Guest Editor
Department of Molecular Medicine, Viale Regina Elena 291, 00161 Rome, Italy
Interests: NK cells; immune surveillance; senescence
Prof. Alessandra Zingoni

E-Mail Website
Guest Editor
Department of Molecular Medicine, Viale Regina Elena 291, 00161 Rome, Italy
Interests: innate immunity; cancer; stress; immunotherapy; DAMPs; extracellular vesicles

Special Issue Information

Dear Colleagues,

Interferons (IFNs) are a family of pleiotropic cytokines, which play a key role in a wide range of biological processes. In addition to the well-described antiviral actions, IFNs were quickly recognized as central coordinators of innate immune responses during tumorigenesis. However, evidence has emerged in recent years suggesting that IFNs may also trigger immune suppressive mechanisms in cancer-promoting malignant progression and resistance to therapies. Depending on the stimulus, IFNs can be produced by almost any cell type, including fibroblasts and leucocytes, as well as cancer cells, through the engagement of distinct pattern recognition receptors (PRRs). In this regard, danger-associated molecular patterns (DAMPs) released upon cellular stress or therapy-induced cell death represent key inducers of type I IFNs in the tumor microenvironment. Among sensing pathways, a major role is played by the cGAS-STING pathway, which detects cytoplasmic DNA after DNA damage. A growing amount of evidence indicates that the cGAS-STING pathway has a role in regulating other important cellular processes such as autophagy, cell survival, and senescence.

For this Special Issue of Biology, we invite authors to submit original research papers, review articles, commentaries, and perspective pieces on recent progress in the broad topic of Type-I-IFNs in cancer diseases, including cancers transformed by an oncogenic virus (i.e., HPV, EBV), highlighting their dichotomous role and the potential therapeutic benefit of type I IFN pathway modulation.

Prof. Alessandra Soriani
Prof. Alessandra Zingoni
Guest Editors

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Keywords

  • Type I interferons
  • cancer
  • innate immunity
  • DAMPs
  • Immunotherapy
  • cGas-STING pathway
  • oncogenic viruses

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Published Papers (4 papers)

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Review

21 pages, 2970 KiB  
Review
Virus-Induced Tumorigenesis and IFN System
by Marco Iuliano, Giorgio Mangino, Maria Vincenza Chiantore, Paola Di Bonito, Paolo Rosa, Elisabetta Affabris and Giovanna Romeo
Biology 2021, 10(10), 994; https://doi.org/10.3390/biology10100994 - 1 Oct 2021
Cited by 5 | Viewed by 3409
Abstract
Oncogenic viruses favor the development of tumors in mammals by persistent infection and specific cellular pathways modifications by deregulating cell proliferation and inhibiting apoptosis. They counteract the cellular antiviral defense through viral proteins as well as specific cellular effectors involved in virus-induced tumorigenesis. [...] Read more.
Oncogenic viruses favor the development of tumors in mammals by persistent infection and specific cellular pathways modifications by deregulating cell proliferation and inhibiting apoptosis. They counteract the cellular antiviral defense through viral proteins as well as specific cellular effectors involved in virus-induced tumorigenesis. Type I interferons (IFNs) are a family of cytokines critical not only for viral interference but also for their broad range of properties that go beyond the antiviral action. In fact, they can inhibit cell proliferation and modulate differentiation, apoptosis, and migration. However, their principal role is to regulate the development and activity of most effector cells of the innate and adaptive immune responses. Various are the mechanisms by which IFNs exert their effects on immune cells. They can act directly, through IFN receptor triggering, or indirectly by the induction of chemokines, the secretion of further cytokines, or by the stimulation of cells useful for the activation of particular immune cells. All the properties of IFNs are crucial in the host defense against viruses and bacteria, as well as in the immune surveillance against tumors. IFNs may be affected by and, in turn, affect signaling pathways to mediate anti-proliferative and antiviral responses in virus-induced tumorigenic context. New data on cellular and viral microRNAs (miRNAs) machinery, as well as cellular communication and microenvironment modification via classical secretion mechanisms and extracellular vesicles-mediated delivery are reported. Recent research is reviewed on the tumorigenesis induced by specific viruses with RNA or DNA genome, belonging to different families (i.e., HPV, HTLV-1, MCPyV, JCPyV, Herpesviruses, HBV, HCV) and the IFN system involvement. Full article
(This article belongs to the Special Issue Type I Interferons: A Double-Edged Sword of Immune Regulation and Cancer Progression)
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18 pages, 1643 KiB  
Review
Actin Cytoskeleton Dynamics and Type I IFN-Mediated Immune Response: A Dangerous Liaison in Cancer?
by Paola Trono, Annalisa Tocci, Martina Musella, Antonella Sistigu and Paola Nisticò
Biology 2021, 10(9), 913; https://doi.org/10.3390/biology10090913 - 14 Sep 2021
Cited by 4 | Viewed by 3510
Abstract
Chronic viral infection and cancer are closely inter-related and are both characterized by profound alteration of tissue homeostasis. The actin cytoskeleton dynamics highly participate in tissue homeostasis and act as a sensor leading to an immune-mediated anti-cancer and anti-viral response. Herein we highlight [...] Read more.
Chronic viral infection and cancer are closely inter-related and are both characterized by profound alteration of tissue homeostasis. The actin cytoskeleton dynamics highly participate in tissue homeostasis and act as a sensor leading to an immune-mediated anti-cancer and anti-viral response. Herein we highlight the crucial role of actin cytoskeleton dynamics in participating in a viral mimicry activation with profound effect in anti-tumor immune response. This still poorly explored field understands the cytoskeleton dynamics as a platform of complex signaling pathways which may regulate Type I IFN response in cancer. This emerging network needs to be elucidated to identify more effective anti-cancer strategies and to further advance the immuno-oncology field which has revolutionized the cancer treatment. For a progress to occur in this exciting arena we have to shed light on actin cytoskeleton related pathways and immune response. Herein we summarize the major findings, considering the double sword of the immune response and in particular the role of Type I IFN pathways in resistance to anti-cancer treatment. Full article
(This article belongs to the Special Issue Type I Interferons: A Double-Edged Sword of Immune Regulation and Cancer Progression)
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28 pages, 1019 KiB  
Review
The Yin and Yang of Type I IFNs in Cancer Promotion and Immune Activation
by Martina Musella, Claudia Galassi, Nicoletta Manduca and Antonella Sistigu
Biology 2021, 10(9), 856; https://doi.org/10.3390/biology10090856 - 1 Sep 2021
Cited by 26 | Viewed by 4961
Abstract
Type I Interferons (IFNs) are key regulators of natural and therapy-induced host defense against viral infection and cancer. Several years of remarkable progress in the field of oncoimmunology have revealed the dual nature of these cytokines. Hence, Type I IFNs may trigger anti-tumoral [...] Read more.
Type I Interferons (IFNs) are key regulators of natural and therapy-induced host defense against viral infection and cancer. Several years of remarkable progress in the field of oncoimmunology have revealed the dual nature of these cytokines. Hence, Type I IFNs may trigger anti-tumoral responses, while leading immune dysfunction and disease progression. This dichotomy relies on the duration and intensity of the transduced signaling, the nature of the unleashed IFN stimulated genes, and the subset of responding cells. Here, we discuss the role of Type I IFNs in the evolving relationship between the host immune system and cancer, as we offer a view of the therapeutic strategies that exploit and require an intact Type I IFN signaling, and the role of these cytokines in inducing adaptive resistance. A deep understanding of the complex, yet highly regulated, network of Type I IFN triggered molecular pathways will help find a timely and immune“logical” way to exploit these cytokines for anticancer therapy. Full article
(This article belongs to the Special Issue Type I Interferons: A Double-Edged Sword of Immune Regulation and Cancer Progression)
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18 pages, 1246 KiB  
Review
Type I Interferons in COVID-19 Pathogenesis
by Enrico Palermo, Daniele Di Carlo, Marco Sgarbanti and John Hiscott
Biology 2021, 10(9), 829; https://doi.org/10.3390/biology10090829 - 26 Aug 2021
Cited by 30 | Viewed by 4565
Abstract
Among the many activities attributed to the type I interferon (IFN) multigene family, their roles as mediators of the antiviral immune response have emerged as important components of the host response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Viruses likewise have [...] Read more.
Among the many activities attributed to the type I interferon (IFN) multigene family, their roles as mediators of the antiviral immune response have emerged as important components of the host response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Viruses likewise have evolved multiple immune evasion strategies to circumvent the host immune response and promote virus propagation and dissemination. Therefore, a thorough characterization of host–virus interactions is essential to understand SARS-CoV-2 pathogenesis. Here, we summarize the virus-mediated evasion of the IFN responses and the viral functions involved, the genetic basis of IFN production in SARS-CoV-2 infection and the progress of clinical trials designed to utilize type I IFN as a potential therapeutic tool. Full article
(This article belongs to the Special Issue Type I Interferons: A Double-Edged Sword of Immune Regulation and Cancer Progression)
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