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Sézary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS. [ABSTRACT FROM AUTHOR]

Abstract: We explored use of the suction‐blister wound model in the assessment of not only epidermal regeneration but also pain, the microvascular response and bacteriology. The effects of topical zinc sulfate were studied to articulate the methodologies in this double‐blind trial. One epidermal suction blister (10 mm) was induced on each buttock in 30 healthy volunteers (15 females:15 males) and deroofed on day 0. The wounds were randomized to daily treatment with 1.4% zinc sulfate shower gel (n = 20), placebo (n = 20) or control (n = 20). Digital photography coupled with planimetry, transepidermal water loss (TEWL) measurement and optical coherence tomography (OCT) was benchmarked to the gold standard of histology of 60 full‐thickness wound biopsies on day 4. Pain increased after application of the shower gels. Microvessel density, determined from OCT images, increased from day 0 to day 2 in the three groups but increased more with the placebo than with the zinc shower gel (p = 0.003) or the control treatment (p = 0.002) and correlated (rS = 0.313, p = 0.015) with the inflammatory response on day 4, as determined by histology. Coagulase‐negative staphylococci were more common in wounds compared with skin (p = 0.002) and was reduced (p = 0.030) with zinc sulfate treatment. Planimetric analysis of digital wound images was not biased (p = 0.234) compared with histology, and TEWL measurements showed no correlation (rS = 0.052, p = 0.691) with epithelialization. Neoepidermal formation, determined by histology, did not differ (p = 0.290) among the groups. Zinc sulfate reduced (p = 0.031) the release of lactate dehydrogenase from cultured gel‐treated keratinocytes isolated from the blister roofs. Therefore, combination of the standardized suction‐blister wound model with noninvasive planimetry and OCT is a useful tool for assessing wound therapies. Zinc sulfate transiently dampened inflammation and reduced bacterial growth. [ABSTRACT FROM AUTHOR]

Interaction between tumour survival tactics and antitumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p = 0.0065). Transforming growth factor (TGF)-β and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3 . T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer. [ABSTRACT FROM AUTHOR]