Type I interferons and dendritic cells in cancer immunotherapy

Sprooten, Jenny; Agostinis, Patrizia; Garg, Abhishek D.

doi:10.1016/bs.ircmb.2019.06.001

Cited by 97 publications

(79 citation statements)

References 230 publications

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“…Novel immunotherapies based on activators of the STING pathways or other endogenous IFN related signals (extensively discussed in other reviews [2,13]) are in an early phase of clinical experimentation and may represent a highly valuable approach for a localized activation of the endogenous IFN-I system to be exploited in cancer therapy. Recent advances have been made also in in vivo targeted delivery of IFN-I by Ab conjugates [60,61].…”

Section: Discussionmentioning

confidence: 99%

“…While the research progress underscores new opportunities to exploit the knowledge on the IFN-I system for the development of biomarkers of response to antitumor therapies, recent studies reveal new targets and mechanisms of action. There are recent and excellent review articles on the antitumor effects of IFN, where emerging areas, such as that of the clinical use of activators of the stimulator of IFN genes (STING) pathway and other endogenous IFN signals have been reviewed and discussed [2,4,13]. However, some of the new mechanisms of action and therapeutic opportunities regarding the use of IFN have not yet been discussed.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Aricò

Castiello

Capone

et al. 2019

Cancers

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“…Radiation-generated dsDNA plays a crucial role activating cGAS/STING signaling pathway in both tumor cells and immune cells [9,42,43]. For example, radiation-activated cGAS/STING mediated tumorsuppressive effects, meanwhile, triggers the capability of DCs and promotes the anti-tumor immunity [44]. In our study, we found that the combination of ICG-001 with radiotherapy led to the activation of cGAS/STING pathway and increased TIL IFN-γ + CD8 + T cells in ltrates in HCC tissues.…”

Section: Discussionmentioning

confidence: 99%

Wnt/β-catenin Inhibitor ICG-001 Enhances the Antitumor Efficacy of Radiotherapy by Increasing Radiation-induced DNA Damage and Improving Tumor Immune Microenvironment in Hepatocellular Carcinoma

Huang

Sheng

Xiao

et al. 2020

Preprint

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Background: Radiotherapy has a promising anti-tumor effect in hepatocellular carcinoma (HCC), depending on the its regulatory effects on both cancer cells and tumor immune microenvironment (TME). Wnt/β-catenin signaling pathway activation, which is one of the most common alterations in HCC patients, has been reported to induce radioresistance, and also create immunosuppressive TME. However, it is unclear whether inhibition of wnt/β-catenin pathway could enhance the treatment efficacy of radiotherapy. In this study, we aim to explore the effect of wnt/β-catenin inhibitor ICG-001 in combination with radiotherapy and the underlying mechanism in HCC.Methods: C57BL/6 and nude mouse subcutaneous tumor models were used to evaluate the efficacy of different treatment regimens in tumor growth control, tumor recurrence inhibition and survival improvement. Flow cytometry was performed to assess the alterations of tumor infiltrating lymphocytes (TILs). Radioresistance was investigated by clone formation assay and γ-H2AX measurements. Wnt/β-catenin and cGAS/STING pathway activation was detected by immunoblotting. Results: The addition of ICG-001 to radiotherapy exhibited better anti-tumor control efficacy in tumor-bearing C57BL/6 mice than nude mice, which suggested that ICG-001 had a critical role in activating TME. The comprehensive analysis of TILs revealed that compared with radiotherapy alone, the combination of ICG-001 with radiotherapy boosted the infiltration and IFN-γ production ability of TIL CD8+ T cells, meanwhile reduced the number of TIL Tregs. Moreover, mechanism study demonstrated that ICG-001 exerted a radiosensitizing effect on HCC cells, thus leading to stronger activation of cGAS/STING signaling pathway upon radiotherapy in vitro and in vivo. Utilization of STING inhibitor, C-176, significantly impaired the synergetic effect of ICG-001 with radiotherapy on tumor control and TME activation. Furthermore, combination therapy led to a stronger immunologic memory and lasting anti-tumor immunity than radiotherapy, thus preventing tumor relapse in HCC tumor-bearing mice.Conclusion: Our findings showed that ICG-001 increased radioresistance and improved TME upon radiotherapy in HCC. Compared with radiotherapy alone, the combination of ICG-001 with radiotherapy displayed better therapeutic efficacy in inhibiting tumor growth, prolonging survival, and preventing recurrence in tumor-bearing mice. These data indicated that ICG-001 might be a potential synergetic treatment for radiotherapy and radioimmunotherapy in HCC.

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“…Herein, specific chemotherapies (e.g., anthracyclines, oxaliplatin), targeted therapies (e.g., bortezomib), physical therapies (e.g., photodynamic therapy, high hydrostatic pressure) and oncolytic viruses have been reported to induce an immunogenic form of apoptosis or immunogenic cell death (ICD) in cancer cells that enables anticancer immunity [54][55][56][57]. ICD-inducing anticancer therapies can achieve this rare pro-immune phenomenon in cancer due to the spatio-temporally defined emission of danger signals (specific 'eat me' or 'find me' signals and alarmins), as well as pathogen-response signals like cytokines (i.e., type I interferons/IFNs) and chemokines (e.g., CCL2, CXCL1 and CXCL10) [54,[58][59][60][61][62]. Although such findings argue for the prioritization of apoptotic ICD for immuno-oncology paradigms, it is clear that ICD can also operate via other forms of RCD such as necroptosis [59,63,64].…”

Section: Introductionmentioning

confidence: 99%

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

Sprooten

Wijngaert

Vanmeerbeek

et al. 2020

Cells

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112

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Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy.

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Type I interferons and dendritic cells in cancer immunotherapy

Cited by 97 publications

References 230 publications

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

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

Wnt/β-catenin Inhibitor ICG-001 Enhances the Antitumor Efficacy of Radiotherapy by Increasing Radiation-induced DNA Damage and Improving Tumor Immune Microenvironment in Hepatocellular Carcinoma

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

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