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  • 1
    Online Resource
    Online Resource
    Modulare Fußgängerbrücken aus seriell hergestellten Betonfertigteilen : Entwürfe aus dem DFG‐Schwerpunktprogramm 2187
    Wiley ; 2023
    In:  Beton- und Stahlbetonbau
    Details
    In: Beton- und Stahlbetonbau, Wiley
    Abstract: Modular footbridges made of serially prefabricated concrete elements – Designs from DFG Priority Programme 2187 Modular building structures enable serial and automated production of prefabricated elements, which can be produced in a controlled manner in a precast concrete plant and then assembled on the construction site in a short time. This allows manufacturing processes to be optimised and new technologies of automated and robot‐assisted production to be used. Off‐site production reduces noise, dust and traffic at construction sites, and the rationalisation of processes in the precast concrete plant can minimise offcuts and waste, thus saving resources. In addition, high‐performance materials can be processed with high precision in an environment protected from the weather, so that their properties are optimally utilised and a high and consistent quality is achieved. From the design engineer, modular construction requires a comprehensive understanding and consideration of manufacturing processes as well as careful planning of all joints of the structure. The design team is faced with the challenge of designing a functional, durable and aesthetically appealing structure despite the demands of modularisation, rationalisation and production. In the design studies presented in this paper, the authors meet this challenge by applying technologies from current research projects in modular concrete construction to a consistent design scenario of a pedestrian bridge.
    Type of Medium: Online Resource
    ISSN: 0005-9900 , 1437-1006
    URL: Article
    DOI: 10.1002/best.202300056
    RVK:
    ZG 1100
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2151239-5
    detail.hit.zdb_id: 240053-4
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  • 2
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    Online Resource
    eHealth Literacy in German Skin Cancer Patients
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 14 ( 2022-07-08), p. 8365-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 14 ( 2022-07-08), p. 8365-
    Abstract: The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patients’ primary sources of health-related information as well as their self-proclaimed eHealth literacy. We received 714 questionnaires. Regardless of age, the primary source of information was the treating dermato-oncologist, followed by the treating general practitioner and the Internet. However, with increasing age, the usage of the Internet decreased. Hence, younger participants were better equipped to find health-related information while using the Internet. Additionally, comprehending health-related information and gaining medical knowledge was significantly increased in better-educated participants. Overall, our study shows that with increased use of eHealth services, accessing web-based information increased, correlating with a better eHealth literacy of our patients. eHealth technologies are increasingly becoming more prevalent as a primary source of information in our modern health care system. Thus, it is crucial to educate cancer patients in eHealth literacy to make autonomous, informed decisions and gain more confidence in dealing with their disease.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19148365
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 3
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    Online Resource
    Systemically Administered TLR7/8 Agonist and Antigen-Conjugated Nanogels Govern Immune Responses against Tumors
    American Chemical Society (ACS) ; 2022
    In:  ACS Nano Vol. 16, No. 3 ( 2022-03-22), p. 4426-4443
    Details
    In: ACS Nano, American Chemical Society (ACS), Vol. 16, No. 3 ( 2022-03-22), p. 4426-4443
    Type of Medium: Online Resource
    ISSN: 1936-0851 , 1936-086X
    URL: Article
    URL: Article
    DOI: 10.1021/acsnano.1c10709
    DOI: 10.1021/acsnano.1c10709.s001
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2022
    detail.hit.zdb_id: 2383064-5
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  • 4
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    Online Resource
    Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 7 ( 2022-03-28), p. 1710-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 7 ( 2022-03-28), p. 1710-
    Abstract: The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment of metastatic melanoma and other tumor types. The currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 and anti-programmed cell death (PD)-1. By this, the T-cell-inhibitory CTLA-4/CD80/86 and PD-1/PD-1L/2L signaling axes are inhibited. This leads to sustained effector T-cell activity and circumvents the immune evasion of tumor cells, which frequently upregulate PD-L1 expression and modulate immune checkpoint molecule expression on leukocytes. As a result, profound clinical responses are observed in 40–60% of metastatic melanoma patients. Despite the pivotal role of T effector cells for triggering anti-tumor immunity, mounting evidence indicates that ICI efficacy may also be attributable to other cell types than T effector cells. In particular, emerging research has shown that ICI also impacts innate immune cells, such as myeloid cells, natural killer cells and innate lymphoid cells, which may amplify tumoricidal functions beyond triggering T effector cells, and thus improves clinical efficacy. Effects of ICI on non-T cells may additionally explain, in part, the character and extent of adverse effects associated with treatment. Deeper knowledge of these effects is required to further develop ICI treatment in terms of responsiveness of patients to treatment, to overcome resistance to ICI and to alleviate adverse effects. In this review we give an overview into the currently known immunomodulatory effects of ICI treatment in immune cell types other than the T cell compartment.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14071710
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
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    Online Resource
    The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 2 ( 2021-01-08), p. 210-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 2 ( 2021-01-08), p. 210-
    Abstract: Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell–cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC–Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13020210
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 6
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    Online Resource
    β2 Integrins on Dendritic Cells Modulate Cytokine Signaling and Inflammation-Associated Gene Expression, and Are Required for Induction of Autoimmune Encephalomyelitis
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 14 ( 2022-07-13), p. 2188-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 14 ( 2022-07-13), p. 2188-
    Abstract: Heterodimeric β2 integrin surface receptors (CD11a-d/CD18) are specifically expressed by leukocytes that contribute to pathogen uptake, cell migration, immunological synapse formation and cell signaling. In humans, the loss of CD18 expression results in leukocyte adhesion deficiency syndrome (LAD-)1, largely characterized by recurrent severe infections. All available mouse models display the constitutive and ubiquitous knockout of either α or the common β2 (CD18) subunit, which hampers the analysis of the cell type-specific role of β2 integrins in vivo. To overcome this limitation, we generated a CD18 gene floxed mouse strain. Offspring generated from crossing with CD11c-Cre mice displayed the efficient knockdown of β2 integrins, specifically in dendritic cells (DCs). Stimulated β2-integrin-deficient splenic DCs showed enhanced cytokine production and the concomitantly elevated activity of signal transducers and activators of transcription (STAT) 1, 3 and 5, as well as the impaired expression of suppressor of cytokine signaling (SOCS) 2–6 as assessed in bone marrow-derived (BM) DCs. Paradoxically, these BMDCs also showed the attenuated expression of genes involved in inflammatory signaling. In line, in experimental autoimmune encephalomyelitis mice with a conditional DC-specific β2 integrin knockdown presented with a delayed onset and milder course of disease, associated with lower frequencies of T helper cell populations (Th)1/Th17 in the inflamed spinal cord. Altogether, our mouse model may prove to be a valuable tool to study the leukocyte-specific functions of β2 integrins in vivo.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11142188
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 7
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    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-4-28)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-4-28)
    Abstract: Effective anti-tumor immune responses are mediated by T cells and require organized, spatially coordinated interactions within the tumor microenvironment (TME). Understanding coordinated T-cell-behavior and deciphering mechanisms of radiotherapy resistance mediated by tumor stem cells will advance risk stratification of oropharyngeal cancer (OPSCC) patients treated with primary chemoradiotherapy (RCTx). Methods To determine the role of CD8 T cells (CTL) and tumor stem cells for response to RCTx, we employed multiplex immunofluorescence stains on pre-treatment biopsy specimens from 86 advanced OPSCC patients and correlated these quantitative data with clinical parameters. Multiplex stains were analyzed at the single-cell level using QuPath and spatial coordination of immune cells within the TME was explored using the R-package Spatstat. Results Our observations demonstrate that a strong CTL-infiltration into the epithelial tumor compartment (HR for overall survival, OS: 0.35; p & lt;0.001) and the expression of PD-L1 on CTL (HR: 0.36; p & lt;0.001) were both associated with a significantly better response and survival upon RCTx. As expected, p16 expression was a strong predictor of improved OS (HR: 0.38; p=0.002) and correlated with overall CTL infiltration (r: 0.358, p & lt;0.001). By contrast, tumor cell proliferative activity, expression of the tumor stem cell marker CD271 and overall CTL infiltration, regardless of the affected compartment, were not associated with response or survival. Conclusion In this study, we could demonstrate the clinical relevance of the spatial organization and the phenotype of CD8 T cells within the TME. In particular, we found that the infiltration of CD8 T cells specifically into the tumor cell compartment was an independent predictive marker for response to chemoradiotherapy, which was strongly associated with p16 expression. Meanwhile, tumor cell proliferation and the expression of stem cell markers showed no independent prognostic effect for patients with primary RCTx and thus requires further study.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1070203
    DOI: 10.3389/fimmu.2023.1070203.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 8
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    Online Resource
    Poliosis Is Associated with Response to Checkpoint-Inhibitor Therapy: A Case Report of Two Patients with Multifocal Metastatic Melanoma
    MDPI AG ; 2022
    In:  Immuno Vol. 2, No. 2 ( 2022-03-31), p. 307-316
    Details
    In: Immuno, MDPI AG, Vol. 2, No. 2 ( 2022-03-31), p. 307-316
    Abstract: The advent of immune-checkpoint inhibitors (ICIs) led to significant improvements in the treatment of patients with advanced melanoma and resulted in durable tumor responses in a considerable number of advanced melanoma patients. Next to the immune-mediated anti-neoplastic effects, ICIs may cause various immune-related adverse events (irAEs), often requiring early discontinuation of therapy. By contrast, cutaneous irAE rarely enforce treatment discontinuation but may represent simple and robust predictive markers for treatment response. The relevance of irAEs as clinical markers for an improved response to immunotherapy is still debated. We report here on two patients with multifocal metastatic melanoma who developed the rare event of generalized poliosis during combined immunotherapy with ipilimumab plus nivolumab, followed by a near-complete and durable response. Our observations suggest that poliosis may be a useful and simple clinical indicator of anti-tumor immunity, clinical response and favorable survival outcome in advanced melanoma patients treated with ICI.
    Type of Medium: Online Resource
    ISSN: 2673-5601
    URL: Article
    DOI: 10.3390/immuno2020020
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 3091938-1
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  • 9
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    Online Resource
    The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 22 ( 2022-11-11), p. 3570-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 22 ( 2022-11-11), p. 3570-
    Abstract: Background and objectives: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphomas, characterized by mature, skin-tropic CD4+ T-helper cells. In order to study the immune tumor microenvironment in MF patients, we performed immunohistochemical stains on MF biopsies, digitized whole-slide tissue sections, and performed quantitative analysis of the different immune cell subsets to correlate tissue parameters with the clinical data of patients, such as progression-free survival or overall survival. Patients and methods: Overall, 35 patients who were treated between 2009 and 2019 and for whom one or more paraffin tissue blocks were available have been included in the present study (58 tissue specimens in total). Conventional immunohistochemistry stains for CD3, CD4, CD8, CD20 and CD30 were used for the analysis of the immune phenotype, and quantitative analysis was performed using QuPath as a quantitative digital pathology tool for bioimage analysis of whole slides. Results: Analysis of tissue parameters for prognostic significance revealed that patients with a stronger infiltration by CD8+ lymphocytes within the tumor cell compartment had a higher risk of disease progression (p = 0.031) and showed a shorter progress-free survival (p = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression (p = 0.023) and progression-free survival (p = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression (p = 0.015) and a shorter progression-free survival (p = 0.032) for older patients ( 〉 61 years) were observed. Conclusions: Our results demonstrated the prognostic relevance of large-cell transformation in mycosis fungoides and its strong association with the presence of CD30+ lymphocytes. Unlike previous reports, our study suggests an adverse prognostic role for CD8+ T cells in patients with mycosis fungoides. Moreover, our data indicate that the immune phenotype within the tumor microenvironment shows strong temporal heterogeneity and is altered in the course of tumor progression.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11223570
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 10
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    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-6-6)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-6-6)
    Abstract: β2-integrins are heterodimeric surface receptors that are expressed specifically by leukocytes and consist of a variable α (CD11a-d) and a common β-subunit (CD18). Functional impairment of CD18, which causes leukocyte adhesion deficiency type-1 results in an immunocompromised state characterized by severe infections, such as invasive pulmonary aspergillosis (IPA). The underlying immune defects have largely been attributed to an impaired migratory and phagocytic activity of polymorphonuclear granulocytes (PMN). However, the exact contribution of β2-integrins for PMN functions in-vivo has not been elucidated yet, since the mouse models available so far display a constitutive CD18 knockout (CD18 -/- or CD18 hypo ). To determine the PMN-specific role of β2-integrins for innate effector functions and pathogen control, we generated a mouse line with a Ly6G-specific knockdown of the common β-subunit (CD18 Ly6G cKO). We characterized CD18 Ly6G cKO mice in-vitro to confirm the PMN-specific knockdown of β2-integrins. Next, we investigated the clinical course of IPA in A. fumigatus infected CD18 Ly6G cKO mice with regard to the fungal burden, pulmonary inflammation and PMN response towards A. fumigatus . Our results revealed that the β2-integrin knockdown was restricted to PMN and that CD18 Ly6G cKO mice showed an aggravated course of IPA. In accordance, we observed a higher fungal burden and lower levels of proinflammatory innate cytokines, such as TNF-α, in lungs of IPA-infected CD18 Ly6G cKO mice. Bronchoalveolar lavage revealed higher levels of CXCL1, a stronger PMN-infiltration, but concomitantly elevated apoptosis of PMN in lungs of CD18 Ly6G cKO mice. E x-vivo analysis further unveiled a strong impairment of PMN effector function, as reflected by an attenuated phagocytic activity, and a diminished generation of reactive oxygen species (ROS) and neutrophil-extracellular traps (NET) in CD18-deficient PMN. Overall, our study demonstrates that β2-integrins are required specifically for PMN effector functions and contribute to the clearance of A. fumigatus by infiltrating PMN, and the establishment of an inflammatory microenvironment in infected lungs.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.823121
    DOI: 10.3389/fimmu.2022.823121.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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