Treatment of in vitro generated Langerhans cells with JAK-STAT inhibitor reduces their inflammatory potential.

Alopecia areata (AA) is a condition in which hair is lost in small regions or over the entire body. It has a prevalence of 1 in 1000 and has a great impact on psychological wellbeing. AA is generally considered an autoimmune disease in which a collapse of the immune privilege system of the hair follicle has shown to play an important role, potentially driven by interferon gamma (IFN-γ). The most prominent cells located in or around the hair follicle in AA are Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells. Langerhans cells, specialized dendritic cells, are resident in the epidermis and are known to associate with hair follicles. Therefore, we aimed to develop in vitro generated Langerhans cells contributing as an in vitro model of disease. In vitro models provide insight into the behaviour of cells and are a valuable tool before being in need of an animal model or patient samples. For this, Langerhans-like cells were generated from CD14+ monocytes in the presence of GM-CSF and TGF-ß. After 10 days of cell culture, Langerhans-like cells express CD207 and CD1a but lack CD209 expression as well as Birbeck granules. Next, Langerhans-like cells were exposed to inflammatory conditions and the effect of different AA treatments was investigated. All treatments-diphencyprone contact immunotherapy, UV-B light therapy and JAK-STAT inhibition-affect the expression of costimulatory and skin-homing markers on Langerhans-like cells. Importantly, also the T cell stimulatory capacity of Langerhans-like cells was significantly reduced following treatment under inflammatory conditions. Noteworthy, JAK-STAT inhibition outperformed conventional AA treatments. In conclusion, our findings demonstrate that in vitro generated Langerhans-like cells can be used as a model of disease. Moreover, JAK-STAT inhibition may become a valuable new approach for the treatment of AA.

Extra-anogenital giant cutaneous squamous cell carcinomas require multidisciplinary management.

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent cancer and the majority of cSCC have a good prognosis. However, a subset of cSCC can progress to advanced disease. We present the first reported case of a giant cSCC located on the breast. In addition, a systematic literature search on extra-anogenital giant (EAG) cSCC was performed using Pubmed and MEDLINE databases. Thirty-one articles could be retained which were relevant for this review. A total of 42 well-described cases were identified. Median age at presentation was 70 years (range 9-100 years). Twenty-four (57%) patients were male, eighteen were female (43%). The estimated median delay of treatment was 12 months (range 1 to >240 months). In 27 patients (64%) the giant cSCC was localized on the neck, face or scalp, 6 on the thoracic wall or back (14%), 4 on the lower limb (10%), 2 on the hip or buttock (5%), 2 on the upper limb (5%), one (2%) on the breast. Tumor stage at presentation was T2, T3 and T4 in respectively 26 (62%), 11 (26%) and 5 (12%) cases. Lymph node metastases were identified in 1 patient (2%) and distant metastases in another patient (2%). In 34 out of 42 cases (81%) primary radical surgical excision was performed, 3 received radiotherapy, 2 chemotherapy and 3 palliative care. In the cases with reported follow-up, four patients (4/30: 13%) died of disease. The treatment of EAG cSCC poses many problems, making a multidisciplinary approach of paramount importance.