Type <scp>I</scp> interferon signature in the initiation of the immune response in vitiligo

Bertolotti, A.; Boniface, Katia; Vergier, Béatrice; Mossalayi, Djavad; Taı̈eb, Alain; Ezzedine, Khaled; Sénéschal, Julien

doi:10.1111/pcmr.12219

Cited by 123 publications

(118 citation statements)

References 51 publications

(58 reference statements)

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“…Flow cytometry of blister fluid in the screening group initially revealed that active lesional sites had a larger infiltrate of CD8 + T cells than non-lesional sites, or when compared to the skin of healthy individuals (Fig 2A and Supplementary Figure 1). We and others reported that skin-infiltrating CD8+ T cells express CXCR3, their receptor, when analyzed by IHC 4,10,21 . Here we found that CD8+ T cells uniformly express CXCR3 in the skin by flow cytometry (Fig 2B), supporting previous results.…”

Section: Resultsmentioning

confidence: 86%

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

Strassner

Rashighi

Refat

et al. 2017

Journal of the American Academy of Dermatology

101

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Background Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. Objective To investigate potential markers of disease activity directly in the skin of vitiligo subjects and healthy subjects. Methods Patient skin was sampled via a modified suction blister technique allowing for minimally invasive, objective assessment of cytokines and T cell infiltrates in interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. Results In screening and validation, CD8+ T cell number and CXCL9 protein concentration were significantly elevated in active lesional compared to non-lesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by ROC analysis. Suction blistering also allowed for phenotyping of the T cell infiltrate, which overwhelmingly expresses CXCR3. Limitations A small number of patients were enrolled for the study, including a single patient to define the treatment response. Conclusion Measuring CXCL9 directly in the skin may be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

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Section: Resultsmentioning

confidence: 86%

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

Strassner

Rashighi

Refat

et al. 2017

Journal of the American Academy of Dermatology

101

View full text Add to dashboard Cite

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“…A similar composite gene expression profile also was predictive of favorable clinical outcome with therapeutic cancer vaccines [19,20]. A gene expression profile including a type I IFN signature has been found to have positive prognostic value in breast cancer [45-47], and also has been identified in patients undergoing the evolution of vitiligo [48]. Together, these correlative data suggested that type I IFN production might be integrally involved with adaptive T cell responses against tumor antigens.…”

Section: Mechanism Of Innate Immune Sensing Driving Spontaneous Adaptmentioning

confidence: 99%

The STING pathway and the T cell-inflamed tumor microenvironment

Woo

Corrales

Gajewski

2015

Trends in Immunology

206

155

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A major subset of patients with advanced solid tumors shows a spontaneous T cell-inflamed tumor microenvironment, which has prognostic import and is associated with clinical response to immunotherapies. As such, understanding the mechanisms governing the generation of spontaneous T cell responses in only a subset of patients is critical for advancing immunotherapeutic approaches further. Here, we discuss characteristics of T cell-inflamed versus non-inflamed tumors, including a type I IFN signature associated with T cell priming against tumor antigens. We review recent findings that have pointed towards the STING pathway of cytosolic DNA sensing as an important innate immune sensing mechanism driving type I IFN production in the tumor context. Knowledge of this pathway is guiding the further development of novel immunotherapeutic strategies.

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“…The type I IFN profile has also been shown to predict favorable clinical responses to therapeutic cancer vaccines (26) and to anthracycline-based chemotherapy in patients with breast carcinoma characterized by poor prognosis (27). Infiltration of plasmacytoid dendritic cells (pDCs; a subpopulation of DCs that produces high amounts of type I IFNs) into the skin lesions of vitiligo patients generates type I IFN and thus drives the activation and recruitment of autoimmune T cells (28). Overall, the link between a type I IFN profile and T cell responses suggests that these cytokines might be involved in the generation of an adaptive T cell response against tumor antigens.…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: Targeting the Stimulator of Interferon Genes (STING) in the Immunotherapy of Cancer

Corrales

Gajewski

2015

Clinical Cancer Research

147

113

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Novel immunotherapy approaches are transforming the treatment of cancer, yet many patients remain refractory to these agents. One hypothesis is that immunotherapy fails because of a tumor microenvironment that fails to support recruitment of immune cells including CD8+ T cells. Therefore, new approaches designed to initiate a de novo anti-tumor immune response from within the tumor microenvironment are being pursued. Recent evidence has indicated that spontaneous activation of the Stimulator of Interferon Genes (STING) pathway within tumor-resident dendritic cells leads to type I interferon (IFN) production and adaptive immune responses against tumors. This pathway is activated in the presence of cytosolic DNA, that is detected by the sensor cyclic-GMP-AMP synthase (cGAS), and generates cyclic GMP-AMP (cGAMP), which binds and activates STING. As a therapeutic approach, intratumoral injection of STING agonists has demonstrated profound therapeutic effects in multiple mouse tumor models, including melanoma, colon, breast, prostate, and fibrosarcoma. Better characterization of the STING pathway in human tumor recognition, and the development of new pharmacologic approaches to engage this pathway within the tumor microenvironment in patients, are important areas for clinical translation.

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Type I interferon signature in the initiation of the immune response in vitiligo

Cited by 123 publications

References 51 publications

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

The STING pathway and the T cell-inflamed tumor microenvironment

Molecular Pathways: Targeting the Stimulator of Interferon Genes (STING) in the Immunotherapy of Cancer

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