Multidisciplinary long-term care and modern surgical treatment of congenital melanocytic nevi - recommendations by the CMN surgery network

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, Netzwerk Navuschirurgie, NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi-stage procedure. Today, the long-term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of removal at any cost no longer holds. Potential treatment-related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus-based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion

KIR3DS1 directs NK cell-mediated protection against human adenovirus infections

Human adenoviruses (HAdVs) are a major cause for disease in children, in particular after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, effective therapies for HAdV infections in immunocompromised hosts are lacking. To decipher immune recognition of HAdV infection and determine new targets for immune-mediated control, we used an HAdV infection 3D organoid system, based on primary human intestinal epithelial cells. HLA-F, the functional ligand for the activating NK cell receptor KIR3DS1, was strongly up-regulated and enabled enhanced killing of HAdV5-infected cells in organoids by KIR3DS1(+) NK cells. In contrast, HLA-A and HLA-B were significantly down-regulated in HAdV5-infected organoids in response to adenoviral E3/glycoprotein 19K, consistent with evasion from CD8(+) T cells. Immunogenetic analyses in a pediatric allo-HSCT cohort showed a reduced risk to develop severe HAdV disease and faster clearance of HAdV viremia in children receiving KIR3DS1(+)/HLA-Bw4(+) donor cells compared with children receiving non-KIR3DS1(+)/HLA-Bw4(+) cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease