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The approval and effectiveness of immune checkpoint inhibitors in head-and-neck squamous cell carcinoma (HNSCC) highlights the role of the immune system in this tumor entity. HNSCCs not only interacts with the immune system in the tumor tissue, but also induce systemic effects that may be additionally influenced by further factors such as the microbiome. Nonetheless, reliable immunological biomarkers that predict treatment response and outcome in HNSCC patients are lacking. The currently available biomarkers are mainly limited to analyses from tumor biopsies, while biomarkers from liquid biopsies, such as peripheral blood are not well-established. Thus, the here presented trial aims to identify interactions of intra-tumoral and systemic immune responses and to define prognostic immune signatures. Consequently, not only samples from the tumor tissue, but also from peripheral blood and the microbiome will be studied/are being evaluated and correlated with the clinical outcome. In this prospective, multi-center trial, 1000 HNSCC patients and 100 patients in the control cohort with non-tumor head-and-neck surgery will be enrolled. The local immune status from of the tumor and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analyzed before and after surgery and after the adjuvant and definitive radio-chemotherapy (RCT). Clinical baseline characteristics and outcome will additionally be collected. Data mining and modelling approaches will finally be applied to identify interactions of local and systemic immune parameters and to define prognostic immune signatures based on the evaluated immune markers. Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in December 2021 (application number 21-440-B). By now, 150 patients have been enrolled in the intervention cohort. The results will be disseminated to the scientific audience and the general public via presentations at conferences and publication in peer-reviewed journals. [ABSTRACT FROM AUTHOR]

The establishment of immunotherapy applying immune checkpoint inhibitors (ICI) has provided an important new option for the treatment of solid malignant diseases. However, different tumor entities show dramatically different responses to this therapy. BCC responds worse to anti-PD-1 ICIs as compared to cSCC. Differential immune checkpoint expression could explain this discrepancy and, therefore, the aim of this study was to analyze activating and inhibitory immune checkpoints in cSCC and BCC tissues. Tissue microarrays of the invasive front as well as the tumor core of BCC and cSCC samples were used to evaluate PD-1, PD-L1, CD28, and CD86 expression and their topographic distribution profiles by chromogenic immunohistochemistry. QuPath was used to determine the labeling index. The expression of PD-1, PD-L1, and CD28 was significantly higher in both the tumor core and the invasive front of cSCC samples as compared to BCC (p < 0.001). In addition, the ratios of PD-L1/CD86 (p < 0.001) and CD28/CD86 (p < 0.001) were significantly higher in cSCC. The invasive front of both tumor entities showed higher expression levels of all immune markers compared to the tumor core in both tumor entities. The significantly higher expression of PD-1, PD-L1, and CD28 in cSCC, along with the predominance of the inhibitory ligand PD-L1 as compared to the activating CD86 in cSCC, provide a potential explanation for the better objective response rates to anti-PD-1 immunotherapy as compared to BCC. Furthermore, the predominant site of interaction between the immune system and the tumor was within the invasive front in both tumor types. [ABSTRACT FROM AUTHOR]

Tomographic reconstruction has been well established as a valuable tool in the analysis of polymer electrolyte fuel cell (PEMFC) electrodes. While forays have been made into applying it to polymer electrolyte water electrolyzer (PEMWE) electrodes, CO2 electrolyzer electrodes are still new ground. Here a tomographic analysis of an electrochemical CO2 reduction gas diffusion electrode by means of focused ion beam scanning electron microscope tomography is presented. The reconstruction shows a porosity of 68%. While most of the porosity is on the nanoscale, a broad tail of micropores is observed in the distribution. The spatial distribution of the pores is nonuniform. The large pores are concentrated in the center of the layer in the through‐plane direction. From the reconstruction, an effective diffusivity factor of 0.5 for the catalyst layer is calculated. The Knudsen number of 0.19 obtained from the later shows that the diffusion is mostly in the bulk regime. Flooding of the catalyst layer is likely to decrease the effective diffusivity factor substantially. [ABSTRACT FROM AUTHOR]

The approval and effectiveness of immune checkpoint inhibitors in head-and-neck squamous cell carcinoma (HNSCC) highlights the role of the immune system in this tumor entity. HNSCCs not only interacts with the immune system in the tumor tissue, but also induce systemic effects that may be additionally influenced by further factors such as the microbiome. Nonetheless, reliable immunological biomarkers that predict treatment response and outcome in HNSCC patients are lacking. The currently available biomarkers are mainly limited to analyses from tumor biopsies, while biomarkers from liquid biopsies, such as peripheral blood are not well-established. Thus, the here presented trial aims to identify interactions of intra-tumoral and systemic immune responses and to define prognostic immune signatures. Consequently, not only samples from the tumor tissue, but also from peripheral blood and the microbiome will be studied/are being evaluated and correlated with the clinical outcome. In this prospective, multi-center trial, 1000 HNSCC patients and 100 patients in the control cohort with non-tumor head-and-neck surgery will be enrolled. The local immune status from of the tumor and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analyzed before and after surgery and after the adjuvant and definitive radio-chemotherapy (RCT). Clinical baseline characteristics and outcome will additionally be collected. Data mining and modelling approaches will finally be applied to identify interactions of local and systemic immune parameters and to define prognostic immune signatures based on the evaluated immune markers. Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in December 2021 (application number 21-440-B). By now, 150 patients have been enrolled in the intervention cohort. The results will be disseminated to the scientific audience and the general public via presentations at conferences and publication in peer-reviewed journals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Donaubauer, Frey, Weber, Allner, Vogl, Almajali, Kuczera, Tamse, Balk, Müller, Eckstein, Zülch, Mogge, Weissmann, Fietkau, Kesting, Iro, Gaipl, Hecht and Gostian.)