Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells

Clark, Rachael A.; Huang, Susan; Murphy, Gëorge F.; Mollet, Ilse; Hijnen, DirkJan; Muthukuru, Manoj; Schanbacher, Carl F.; Edwards, Vonetta L.; Miller, Danielle M.; Kim, Jenny E.; Lambert, Jo; Kupper, Thomas S.

doi:10.1084/jem.20071190

Cited by 206 publications

(211 citation statements)

References 68 publications

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“…The induction of this T cell subtype by activin A has also been confirmed in a mouse model of allergic airway disease (Semitekolou et al, 2009). An important role of Tregs in the pathogenesis of human skin cancer appears probable, as they have been shown to infiltrate human squamous cell carcinomas and to be at least partly responsible for the evasion of the host immune response by these tumours (Clark et al, 2008).…”

Section: A Functional Role Of Activin In Skin Cancermentioning

confidence: 99%

The bright and the dark sides of activin in wound healing and cancer

Antsiferova

Werner

2012

Journal of Cell Science

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SummaryActivin was initially described as a protein that stimulates release of follicle stimulating hormone from the pituitary, and it is well known for its important roles in different reproductive functions. In recent years, this multifunctional factor has attracted the attention of researchers in other fields, as new functions of activin in angiogenesis, inflammation, immunity, fibrosis and cancer have been discovered. Studies from our laboratory have identified activin as a crucial regulator of wound healing and skin carcinogenesis. On the one hand, it strongly accelerates the healing process of skin wounds but, on the other hand, it enhances scar formation and the susceptibility to skin tumorigenesis. Finally, results from several laboratories have revealed that activin enhances tumour formation and/ or progression in some other organs, in particular through its effect on the tumour microenvironment, and that it also promotes cancerinduced bone disruption and muscle wasting. These findings provide the basis for the use of activin or its downstream targets for the improvement of impaired wound healing, and of activin antagonists for the prevention and treatment of fibrosis and of malignant tumours that overexpress activin. Here, we summarize the previously described roles of activin in wound healing and scar formation and discuss functional studies that revealed different functions of activin in the pathogenesis of cancer. The relevance of these findings for clinical applications will be highlighted.

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Section: A Functional Role Of Activin In Skin Cancermentioning

confidence: 99%

The bright and the dark sides of activin in wound healing and cancer

Antsiferova

Werner

2012

Journal of Cell Science

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“…Stress-Free Therapy ® ) can serve as not only a potent therapy to treat existing inflammatory diseases but also to prevent the ignition of autoimmune diseases. Meanwhile, the prolonged duration of the B reg cell activation and IL-10 expression in major lymphocytes observed in latter SF sessions might not be welcomed, because, ectopic and/or prolonged suppression of inflammatory responses can deteriorate the prognosis of cancer patients [27][28][29] . However, obvious down-regulation of activated B reg cells and IL-10 expressing lymphocytes and slight increase of IL-17A expressing CD4 + T cell subpopulations after the second SF session ( Figure 3C) suggest an 'balanced' regulation of systemic immune responses improved by repetitive PP-LILI stimuli.…”

Section: Discussionmentioning

confidence: 99%

Effect of Stress-Free Therapy on immune system: Induction of Interleukin 10 expression in lymphocytes through activation of CD19(+) CD24(hi) CD38(hi) regulatory B Cells

et al. 2015

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Background and aims:Mild thermal treatment with "Pinpoint Plantar Long-wavelength Infrared Light Irradiation (PP-LILI)" named as Stress-Free Therapy ® increases peripheral-deep body temperature and blood flow, and improves multiple disorders including hyperpiesia, type II diabetes and cardiovascular patients. Immunomodulatory effects of PP-LILI were investigated. Materials and methods: Seven healthy individuals and 4 people with underlying medical condition (UMC) participated in this study. Participants were given PP-LILI stimuli twice a week over 3 weeks and followed with placebo stimuli over 3 weeks. This set of sessions was repeated 3 times. For analyses, fresh peripheral mononuclear cells from participants were stained with fluorescencedye conjugated monoclonal antibodies and changes in populational compositions and IL-10 expression levels were observed by flow cytometry. Results: Distinct expression of IL-10 in lymphocytes was induced by PP-LILI from the second session in the healthy individuals. This induction was terminated during the following placebo sessions. PP-LILI induced activation of CD19 + CD24 hi CD38 hi regulatory B cells in every session prior to induce the IL-10 in major lymphocytes. Activated regulatory B cells in the individuals with UMC decreased as same levels of healthy individuals after second PP-LILI session and re-activated with the stimuli. Significant population changes in neither regulatory T cells nor proinflammatory IL-17A expressing CD4 + T cells were observed. Conclusions: PP-LILI is a potent immunomodulatory inducer that activates regulatory B cells and consequent IL-10 expression in lymphocytes. Moreover, its stimulatory intervals down-regulate the higher activation of regulatory B cells and lymphocyte's IL-10 expression occurred by UMC to the healthy people's level.

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“…Low expression in melanomas was associated with an absence of ESL + CD8 T-cells (162 also reduced compared to entry into SC tumors in wild-type mice, while blockade of P-selectin/PSL interactions with a recombinant P-selectin fusion protein had no effect. Thus, ESL/E-selectin interactions enable effector CD8 T-cell entry into skin-associated tumors where E-selectin is expressed on the vasculature.…”

Section: A Trafficking Of Effector T-cells Into Tissuesmentioning

confidence: 92%

“…Previous studies have pointed to a low level of HR ligand expression on poorly immunogenic tumors (162,176,219). When expression is augmented using pro-inflammatory stimuli, these molecules facilitate, or are at least While elevated expression of CD44 is a marker of T-cell activation and memory, its role in T-cell entry into tissues has been evaluated in only a small number of studies.…”

Section: Madcam-1 Does Not Mediate 47mentioning

confidence: 99%

Effector CD8 T-cell Entry into Subcutaneous and Intraperitoneal B16 Melanoma Tumors

Woods¹

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Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells

Cited by 206 publications

References 68 publications

The bright and the dark sides of activin in wound healing and cancer

The bright and the dark sides of activin in wound healing and cancer

Effect of Stress-Free Therapy on immune system: Induction of Interleukin 10 expression in lymphocytes through activation of CD19(+) CD24(hi) CD38(hi) regulatory B Cells

Effector CD8 T-cell Entry into Subcutaneous and Intraperitoneal B16 Melanoma Tumors

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