Photoprotection in Patients after Kidney Transplantation Author: Zuzana Hajšelová Tutor: doc. PharmDr. Josef Malý, PhD. Consultant: Mgr. Barbora Vaňková Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradci Králové, Charles University Introduction and aims: Patients after kidney transplantation (KT) are in a higher risk of developing skin cancer as a result of lifelong immunosuppressive (IS) therapy. Thorough photoprotection is therefore recommended. The aim of this study was to determine patients' awareness and level of photoprotection and to analyse selected risk factors for skin cancer development in patients after KT. Methods: The cross-sectional study was undertaken from 15th April to 31st December 2019 at the Haemodialysis Centre in the Teaching Hospital Hradec Králové. Patients included in this study were above 18 years old, who visited Haemodialysis Centre in the defined period. The data was collected from the patients' medical documentation (e.g. occurrence of skin cancer and skin cancer type, current IS) and from the written version of questionnaires (e.g. phototype, sun exposure, photoprotection). The data was analysed using descriptive statistics. Results: There were 410 KT patients in regular care of the Haemodialysis Centre, 361 fulfilled the questionnaire (88.0...

Risk of skin cancer and lymphoproliferative diseases in patients after kidney transplantation Author: Kristína Sidorová Tutor: doc. PharmDr. Josef Malý, Ph.D. Consultant: Mgr. Barbora Vaňková Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction and aims: Organ transplantations (Tx) are associated with the lifelong use of immunosuppressive therapy (IS), which carries with it, among other risks, an increased incidence of malignancies. The most common malignancies after Tx are skin tumors, post-transplant lymphoproliferative diseases (PTLD) are also more common in transplant patients. The aim of the study was to determine the incidence of skin tumors and PTLD in patients with kidney Tx within one transplant center and to analyze the risk factors associated with these diseases. Methods: Retrospective longitudinal study was conduted in the Teaching Hospital Hradec Králové. The study included patients from the age of 18 who had overcome kidney Tx until 24 April 2019, were registered in a transplant clinic in Hradec Králové and had a medical record in the hospital information system. Data collection from medical records took place from 15 April 2019 to 31 December 2019. Collected data included demographic characteristics, family history,...

Selon les facteurs solubles de l’environnement (cytokines), les monocytes peuvent se différencier en macrophages (Mφ) ou en cellules dendritiques. Mes travaux de thèse montrent que l’IL-34, un second ligand du M-CSF-R (c-fms ou CD115), induit la différenciation de monocytes humains en macrophages CD14+ CD163+ (IL-34-Mφ), phénotypiquement et fonctionnellement similaires aux M-CSF-Mφ et aux macrophages associés aux tumeurs (TAM) isolés du cancer de l’ovaire. Ils possèdent des propriétés immunosuppressives et diminuent la prolifération des lymphocytes T CD4+ activés. Comme les Mφ orchestrent la réponse immunitaire, j’ai évalué la capacité des M-CSF-Mφ, IL-34-Mφ et des TAM à polariser les LT CD4+ mémoires. Les résultats montrent qu’ils polarisent des LT non-Th17 mémoires en LTh17 CCR4+ CCR6+ CD161+ conventionnels exprimant ou non de l’IFN. Ce processus est médié par l’expression constitutive de l’IL-1α membranaire exprimées sur ces macrophages.Dans le but d’identifier des stratégies pour prévenir l’accumulation de ces Mφ dans le cancer, j’ai montré que (i) l’IFNγ et le GM-CSF inhibent la différenciation des M-CSF-Mφ et IL-34-Mφ et que (ii) l’IFNγ permet la réversion des M-CSF-Mφ et IL-34-Mφ en Mφ immunostimulants. En conclusion, mes travaux montrent que les M-CSF-Mφ, IL-34-Mφ et les TAM, considérés initialement comme anti-inflammatoires, induisent la génération de lymphocytes Th17 via une expression constitutive de l’IL-1α. Ce processus pourrait contribuer à maintenir, localement, une inflammation modérée nécessaire au développement tumoral. / According to the soluble factors in the environment (cytokines), monocytes differentiate into macrophages (Mϕ) or dendritic cells. This project demonstrates that IL-34, a second ligand of the M-CSF receptor (c-fms or CD115), induces the differentiation of human monocytes into CD14high CD163 high Mφ (IL-34-Mφ), phenotypically and functionally similar to M-CSF-Mφ and to tumorassociated macrophages (TAM) isolated from the ovarian cancer. They exhibit potent immunosuppressive properties and decrease the proliferation of stimulated Tcells. As Mφ orchestrate the immune response, I have evaluated the capacity of M-CSF-Mφ, IL-34-Mφ and TAM to polarize human memory CD4+ T cells. Unexpectedly, results showed that they switch non- Th17 memory CD4+ T cells into conventional CCR4+ CCR6+ CD161+ Th17 cells, expressing or not IFNγ. This process is mediated by the constitutive expression of membrane IL-1α on these Mϕ subsets. In an attempt to identify strategies to prevent an accumulation of immunomodulatory Mϕ in cancer, I have shown that (i) IFNγ and GM-CSF prevent M-CSFandIL-34-induced monocyte differentiation into immunosuppressive Mφ and (ii) that IFNγ switchesestablished M-CSF-Mφ and IL-34-Mφ into immunostimulatory Mφ. In conclusion, this study demonstrates that human MCSF- Mφ, IL-34-Mφ and TAM initially considered as antiinflammatorycells, induce in vitro Th17 cell generation via a constitutive expression of membrane IL-1α. This process may contribute to maintain locally a restrained and smoldering inflammation required for angiogenesis and metastasis in tumors.