STING-Dependent Interferon-λ1 Induction in HT29 Cells, a Human Colorectal Cancer Cell Line, After Gamma-Radiation

Chen, Jianzhou; Markelc, Boštjan; Kaeppler, Jakob; Ogundipe, Vivian M.L.; Cao, Yuze; McKenna, W. Gillies; Muschel, Ruth J.

doi:10.1016/j.ijrobp.2018.01.091

Cited by 19 publications

(21 citation statements)

References 50 publications

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“…For example, radiotherapy (20 Gy) evoked innate immune sensing dominated by the STING pathway in a MC38 tumor murine model, further driving the adaptive immune response to radiation [126]. Exposure to gamma rays (6 Gy) directly induced type III IFNs mediated by the STING signaling axis in HT29 colorectal tumor cells [127]. Chemotherapies can induce DNA damage and inhibit DNA repair simultaneously; damaged DNA then activates the cGAS-STING axis to potentiate DC-mediated antigen presentation and T-cell priming [129,144].…”

Section: Indirect Sting Agonistsmentioning

confidence: 99%

Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy

et al. 2020

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Cellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.

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Section: Indirect Sting Agonistsmentioning

confidence: 99%

Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy

et al. 2020

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“…We demonstrated that DNA damage causes a pronounced upregulation of IFNL1 in Hut78 and MyLa2000 cells and, to a lesser extent, in SeAx and HaCaT cells. Previously, it has been demonstrated that STING activation can induce interferon expression following DNA damage [10,36]. Therefore, we asked if the STING pathway links 8-MOP + UVA-mediated DNA damage with interferon expression in CTCL.…”

Section: Ifnl1 Activation Following Dna Damage Is Sting-dependentmentioning

confidence: 95%

“…Apart from interfering with viral infections, interferons exhibit proapoptotic and immunomodulating effects (reviewed by [9]). Interestingly, it has recently been shown that chemo-and radiotherapy may "mimic" viral infection through cytoplasmic DNA accumulation, which also induces interferon expression in a STING-dependent manner [10,11].…”

Section: Interferon Signalingmentioning

confidence: 99%

“…Analysis of the IFNL1 expression as a function of time showed that, in Hut78 cells, IFNL1 expression peaked around 24 h after 8-MOP + UVA treatment and then decreased, almost reaching basal levels after 72 h ( Figure 2C). Previously, the activation of inflammatory signaling at three-five days following the genetic insult was reported [10,11] and ascribed rather to micronuclei formation than an immediate response to DNA damage. Micronuclei result from perturbed mitosis when cells with unrepaired or aberrantly repaired DNA breaks progress through mitosis.…”

Section: Expression Of Ifnl1 Is Related To Dna Damagementioning

confidence: 99%

“…Tank-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) have been reported to operate downstream from STING [5]. Moreover, Chen et al showed that STING-dependent IFNL1 production is also controlled by IRF1 in response to radiation [10]. To test if these factors are also active in our setting, we downregulated them with specific siRNAs (targeting TBK1, IRF3 and IRF1) or blocked with chemical inhibitors (TBK1), using IFNL1 mRNA levels as a marker of downstream pathway functionality.…”

Section: Ifnl1 Activation Following Dna Damage Is Sting-dependentmentioning

confidence: 99%

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Photochemotherapy Induces Interferon Type III Expression via STING Pathway

Biskup

Larsen

Rib

et al. 2020

Cells

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DNA-damaging cancer therapies induce interferon expression and stimulate the immune system, promoting therapy responses. The immune-activating STING (Stimulator of Interferon Genes) pathway is induced when DNA or double-stranded RNA (dsRNA) is detected in the cell cytoplasm, which can be caused by viral infection or by DNA damage following chemo- or radiotherapy. Here, we investigated the responses of cutaneous T-cell lymphoma (CTCL) cells to the clinically applied DNA crosslinking photochemotherapy (combination of 8–methoxypsoralen and UVA light; 8–MOP + UVA). We showed that this treatment evokes interferon expression and that the type III interferon IFNL1 is the major cytokine induced. IFNL1 upregulation is dependent on STING and on the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS). Furthermore, 8–MOP + UVA treatment induced the expression of genes in pathways involved in response to the tumor necrosis factor, innate immune system and acute inflammatory response. Notably, a subset of these genes was under control of the STING–IFNL1 pathway. In conclusion, our data connected DNA damage with immune system activation via the STING pathway and contributed to a better understanding of the effectiveness of photochemotherapy.

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Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling

Fischer

Lin

Heidegger

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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STING-Dependent Interferon-λ1 Induction in HT29 Cells, a Human Colorectal Cancer Cell Line, After Gamma-Radiation

Cited by 19 publications

References 50 publications

Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy

Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy

Photochemotherapy Induces Interferon Type III Expression via STING Pathway

Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling

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