The important role of CD8+ T-cells in the pathogenesis of psoriasis is well-determined. However, besides type 1 cytokines that were formerly known, it was recently found that these cells secrete type 17 and type 22 cytokines. The majority of IL-17A+CD8+ T-cells in the blood belong to a subset of innate T-cells named mucosa-associated invariant T-cells (MAIT). However, the majority of IL-17A+CD8+ T-cells in psoriatic epidermis are conventional T-cells and are up-regulated in psoriasis. In contrast to Th17 cells that secrete only IL-17, Tc17 cells secrete IFN-ϒ, TNF-α, CCL20, IL-22, and granzyme B as well. The key cytokine is IL-17A, which promotes keratinocyte hyperproliferation and stimulates them to produce other proinflammatory cytokines. These activities initiate and propagate the inflammation and architectural changes in the skin that clinically manifest as psoriatic lesions. However, a relatively novel cell subtype named Tc22 has been discovered in psoriasis that could secrete IL-22 in the absence of IL-17 and IFN-gamma. IL-22 stimulates proliferation and de-differentiation of keratinocytes, subsequently leading to epidermal acanthosis. As the understanding of the pathogenesis of psoriasis increases, the new selective therapies may offer an optimal balance between increased clinical benefit and reduced risk of side-effects.
CD8+ T 细胞在银屑病发病机制中的重要作用已被充分确定。然而,除了以前已知的 1 型细胞因子外,最近还发现这些细胞能分泌 17 型和 22 型细胞因子。血液中的大多数 IL-17A+CD8+ T 细胞属于先天性 T 细胞亚群,被命名为粘膜相关不变性 T 细胞(MAIT)。然而,银屑病表皮中的大多数 IL-17A+CD8+ T 细胞是传统 T 细胞,在银屑病中上调。与只分泌 IL-17 的 Th17 细胞不同,Tc17 细胞也分泌 IFN-ϒ、TNF-α、CCL20、IL-22 和颗粒酶 B。关键的细胞因子是 IL-17A,它能促进角质形成细胞的过度增殖,并刺激它们产生其他促炎细胞因子。这些活动引发并加剧了皮肤的炎症和结构变化,临床上表现为银屑病皮损。然而,在银屑病中发现了一种名为 Tc22 的相对新颖的细胞亚型,它可以在没有 IL-17 和 IFN-gamma 的情况下分泌 IL-22。IL-22 可刺激角朊细胞增殖和去分化,进而导致表皮棘层增生。随着对银屑病发病机理认识的加深,新的选择性疗法可能会在增加临床疗效和降低副作用风险之间实现最佳平衡。
{"title":"The Role of CD8+ T-Cells and their Cytokines in the Pathogenesis of Psoriasis.","authors":"Iva Volarić, Marijana Vičić, Larisa Prpić-Massari","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The important role of CD8+ T-cells in the pathogenesis of psoriasis is well-determined. However, besides type 1 cytokines that were formerly known, it was recently found that these cells secrete type 17 and type 22 cytokines. The majority of IL-17A+CD8+ T-cells in the blood belong to a subset of innate T-cells named mucosa-associated invariant T-cells (MAIT). However, the majority of IL-17A+CD8+ T-cells in psoriatic epidermis are conventional T-cells and are up-regulated in psoriasis. In contrast to Th17 cells that secrete only IL-17, Tc17 cells secrete IFN-ϒ, TNF-α, CCL20, IL-22, and granzyme B as well. The key cytokine is IL-17A, which promotes keratinocyte hyperproliferation and stimulates them to produce other proinflammatory cytokines. These activities initiate and propagate the inflammation and architectural changes in the skin that clinically manifest as psoriatic lesions. However, a relatively novel cell subtype named Tc22 has been discovered in psoriasis that could secrete IL-22 in the absence of IL-17 and IFN-gamma. IL-22 stimulates proliferation and de-differentiation of keratinocytes, subsequently leading to epidermal acanthosis. As the understanding of the pathogenesis of psoriasis increases, the new selective therapies may offer an optimal balance between increased clinical benefit and reduced risk of side-effects.</p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"27 3","pages":"159-162"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirjam Rogl Butina, Igor Švab, Barbara Perić, Igor Bartenjev
Aim of this study was to investigate changes in health behavior of melanoma survivors with emphasis on safe sun behavior (SSB) and skin self-examination (SSE). We also identified factors with significant impact on SSE improvement. We performed a cross-sectional (epidemiological) survey based on a structured questionnaire. 150 patients from three medical institutions were invited and 144 patients responded. Statistical analysis was performed with SPSS version 23.0, with the level of significance set to 0.05. After being diagnosed with cutaneous melanoma, patients significantly improved preventive health behavior: 68.1% showed improvement in SSE, and 91.5% of patients improved SSB. There was statistically significant (P<0.001) improvement in the frequency of skin examination, examination of poorly visible areas (between the toes, genitals), and obtaining help in examination. Use of melanoma images remained scarce. Results for SSB were even better, and statistically significant improvement was recorded in all areas: using higher UV protection filters, wearing sunglasses, headgear, long sleeves, and trousers, and especially in staying in deep shade during hours of heavy UV radiation. The only factor with a positive influence on expected improvement in SSE was female gender. On the other hand, there were two factors that had a negative impact on SSE: patients with melanoma stage 1 and patients who had already self-examined themselves before their melanoma diagnosis. Preventive health behavior improved significantly after diagnosis of cutaneous melanoma. Patients markedly improved SSB and substantially enhanced SSE. We believe that it is reasonable to improve SSE further, encouraging patients by increasing their feeling of self-efficacy.
{"title":"Health Behavior Changes in Cutaneous Melanoma Survivors.","authors":"Mirjam Rogl Butina, Igor Švab, Barbara Perić, Igor Bartenjev","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Aim of this study was to investigate changes in health behavior of melanoma survivors with emphasis on safe sun behavior (SSB) and skin self-examination (SSE). We also identified factors with significant impact on SSE improvement. We performed a cross-sectional (epidemiological) survey based on a structured questionnaire. 150 patients from three medical institutions were invited and 144 patients responded. Statistical analysis was performed with SPSS version 23.0, with the level of significance set to 0.05. After being diagnosed with cutaneous melanoma, patients significantly improved preventive health behavior: 68.1% showed improvement in SSE, and 91.5% of patients improved SSB. There was statistically significant (P<0.001) improvement in the frequency of skin examination, examination of poorly visible areas (between the toes, genitals), and obtaining help in examination. Use of melanoma images remained scarce. Results for SSB were even better, and statistically significant improvement was recorded in all areas: using higher UV protection filters, wearing sunglasses, headgear, long sleeves, and trousers, and especially in staying in deep shade during hours of heavy UV radiation. The only factor with a positive influence on expected improvement in SSE was female gender. On the other hand, there were two factors that had a negative impact on SSE: patients with melanoma stage 1 and patients who had already self-examined themselves before their melanoma diagnosis. Preventive health behavior improved significantly after diagnosis of cutaneous melanoma. Patients markedly improved SSB and substantially enhanced SSE. We believe that it is reasonable to improve SSE further, encouraging patients by increasing their feeling of self-efficacy.</p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"27 2","pages":"67-74"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Today, the scientific community is focusing on the prognostic significance of different histological subtypes of thin melanoma (1). The current staging system for melanoma of the American Joint Committee on Cancer (AJCC) uses Breslow thickness as the primary attribute: melanomas with up to 1 mm thickness is defined as thin, because they present a good prognosis after surgical excision, with a 10-year survival rate of 85-90% in case of a tumor-free margin ≥1 cm (2). There is a significant interaction between mitotic rate and Breslow depth, so the predictive value of the mitotic rate on sentinel lymph node (SLN) positivity can be dependent on Breslow thickness (3). Cutaneous melanoma generally evolves through three clearly discernible progression stages. At first, transformed melanocytes proliferate above the epidermal basement membrane (the in situ or epidermal radial growth phase); they then invade the papillary dermis (the micro-invasive radial growth phase); and subsequently acquire the capacity to grow as a well-known malignant tumor (the invasive vertical growth phase). More specifically, micro-invasive melanoma is a non-tumorigenic radial growth phase of cutaneous melanoma, which invades the superficial dermis without forming a tumor nodule or papule, in absence of regression (3). In contrast, the micro-invasive radial growth phase of cutaneous melanoma with regression will rarely metastasize and, for this reason, the lesion should be recognized and could also be categorized as a 'micro-invasive radial growth phase of uncertain tumorigenic potential' (4). The early vertical growth phase of tumorigenic melanoma is characterized by the presence of a cell cluster in the dermis that is larger than the largest cluster in the epidermis (5). This feature is typical of tumorigenicity, while the mitogenicity is documented by the observation of mitotic figures in dermal melanoma cells (5,6). The early vertical growth phase and the radial growth phase with regression have a statistical chance of distant metastases (7). Therefore, thin melanoma includes four main histological subtypes, which reflect a specific biological behavior: the in situ epidermal radial growth phase, the non-tumorigenic micro-invasive radial growth phase, the micro-invasive radial growth phase with regression of uncertain tumorigenic potential, and the tumorigenic early vertical growth phase. In conclusion, thin melanoma can be considered a generic term and its subtypes should be histologically distinguished beyond its site of origin (acral versus non-acral) because they have different prognostic relevance.
{"title":"Thin Melanoma: A Generic Term Including Four Histological Subtypes of Cutaneous Melanoma.","authors":"Luca Roncati, Teresa Pusiol, Francesco Piscioli","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Today, the scientific community is focusing on the prognostic significance of different histological subtypes of thin melanoma (1). The current staging system for melanoma of the American Joint Committee on Cancer (AJCC) uses Breslow thickness as the primary attribute: melanomas with up to 1 mm thickness is defined as thin, because they present a good prognosis after surgical excision, with a 10-year survival rate of 85-90% in case of a tumor-free margin ≥1 cm (2). There is a significant interaction between mitotic rate and Breslow depth, so the predictive value of the mitotic rate on sentinel lymph node (SLN) positivity can be dependent on Breslow thickness (3). Cutaneous melanoma generally evolves through three clearly discernible progression stages. At first, transformed melanocytes proliferate above the epidermal basement membrane (the in situ or epidermal radial growth phase); they then invade the papillary dermis (the micro-invasive radial growth phase); and subsequently acquire the capacity to grow as a well-known malignant tumor (the invasive vertical growth phase). More specifically, micro-invasive melanoma is a non-tumorigenic radial growth phase of cutaneous melanoma, which invades the superficial dermis without forming a tumor nodule or papule, in absence of regression (3). In contrast, the micro-invasive radial growth phase of cutaneous melanoma with regression will rarely metastasize and, for this reason, the lesion should be recognized and could also be categorized as a 'micro-invasive radial growth phase of uncertain tumorigenic potential' (4). The early vertical growth phase of tumorigenic melanoma is characterized by the presence of a cell cluster in the dermis that is larger than the largest cluster in the epidermis (5). This feature is typical of tumorigenicity, while the mitogenicity is documented by the observation of mitotic figures in dermal melanoma cells (5,6). The early vertical growth phase and the radial growth phase with regression have a statistical chance of distant metastases (7). Therefore, thin melanoma includes four main histological subtypes, which reflect a specific biological behavior: the in situ epidermal radial growth phase, the non-tumorigenic micro-invasive radial growth phase, the micro-invasive radial growth phase with regression of uncertain tumorigenic potential, and the tumorigenic early vertical growth phase. In conclusion, thin melanoma can be considered a generic term and its subtypes should be histologically distinguished beyond its site of origin (acral versus non-acral) because they have different prognostic relevance.</p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"24 4","pages":"169-174"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Calponin is an actin filament-associated protein significantly involved in the regulation of the cellular motility. Some data have indicated that overproduction of calponin in basal cell carcinoma (BCC) of the skin may be responsible for local tumor invasiveness and more aggressive biological behavior. We studied the immunohistochemical expression of calponin in a set of cutaneous BCCs, in order to clarify whether the presence of calponin in cancer cells may be a predictor of invasive tumor growth. The study group consisted of 37 primary BCCs categorized into a non-infiltrative subgroup (5 superficial, 16 nodular subtypes) and infiltrative subgroup (9 nodular-infiltrative, 7 infiltrative subtypes). A specific monoclonal antibody against calponin was used for staining. Expression of calponin in tumor tissue was found in 72.9% (27/37) of the cases, though staining intensity was relatively weak. In superficial, nodular, nodular-infiltrative, and infiltrative BCC subtypes, calponin positivity was found in 80% (4/5), 75% (12/16), 66.7% (6/9), and 71.5% (5/7), respectively. We did not confirm a significant correlation between expression of calponin and given, non-infiltrative, and infiltrative BCC subgroups. Furthermore, we found seven BCCs (18.9%) with striking immunoreactivity for calponin in adjacent peritumorous stroma. There was a significant association between stromal immunoreactivity for calponin and tumor growth histomorphology being positive only in BCCs with infiltrative growth features. Our study has shown that neoplastic cells in cutaneous BCC commonly produce calponin regardless of histological subtype. Expression of calponin in tumor tissue was not associated with the aggressive tumor phenotype. However, since some BCCs with infiltrative growth patterns strongly expressed calponin in peritumorous stroma, this finding could more reliably reflect the biological behavior of cancer and should be better explained in the future.
{"title":"Immunohistochemical Expression of Calponin in Cutaneous Basal Cell Carcinoma.","authors":"Vladimír Bartoš, Milada Kullová","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Calponin is an actin filament-associated protein significantly involved in the regulation of the cellular motility. Some data have indicated that overproduction of calponin in basal cell carcinoma (BCC) of the skin may be responsible for local tumor invasiveness and more aggressive biological behavior. We studied the immunohistochemical expression of calponin in a set of cutaneous BCCs, in order to clarify whether the presence of calponin in cancer cells may be a predictor of invasive tumor growth. The study group consisted of 37 primary BCCs categorized into a non-infiltrative subgroup (5 superficial, 16 nodular subtypes) and infiltrative subgroup (9 nodular-infiltrative, 7 infiltrative subtypes). A specific monoclonal antibody against calponin was used for staining. Expression of calponin in tumor tissue was found in 72.9% (27/37) of the cases, though staining intensity was relatively weak. In superficial, nodular, nodular-infiltrative, and infiltrative BCC subtypes, calponin positivity was found in 80% (4/5), 75% (12/16), 66.7% (6/9), and 71.5% (5/7), respectively. We did not confirm a significant correlation between expression of calponin and given, non-infiltrative, and infiltrative BCC subgroups. Furthermore, we found seven BCCs (18.9%) with striking immunoreactivity for calponin in adjacent peritumorous stroma. There was a significant association between stromal immunoreactivity for calponin and tumor growth histomorphology being positive only in BCCs with infiltrative growth features. Our study has shown that neoplastic cells in cutaneous BCC commonly produce calponin regardless of histological subtype. Expression of calponin in tumor tissue was not associated with the aggressive tumor phenotype. However, since some BCCs with infiltrative growth patterns strongly expressed calponin in peritumorous stroma, this finding could more reliably reflect the biological behavior of cancer and should be better explained in the future. </p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"23 4","pages":"254-9"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}