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Abstract VO2 is a promising phase change material offering a large contrast of electric, thermal, and optical properties when transitioning from semiconductor to metallic phase. Here we show that a hybrid metamaterial obtained by proper combination of a VO2 layer and a nanodisk gold array provides a tunable plasmonic gap resonance in the infrared range. Specifically, we have designed and fabricated a metal–insulator-metal gap resonance by inserting sub-wavelength VO2 film between a flat gold layer and a gold nanodisk resonator array. The resonance of the hybrid metamaterial is centered in the useful 3–5 μm range when VO2 is in its semiconductor state. The experimental study highlights a monotonical spectral tuning of the resonance when increasing temperature up to 50 °C above the room temperature, providing a continuous resonance shift of almost 1 μm in the mid-infrared range. Wavelength range and intensity tunability can be further optimized by modifying the thicknesses of the layers and metamaterial parameters.

Abstract Vanadium dioxide has attracted much interest due to the drastic change of the electrical and optical properties it exhibits during the transition from the semiconductor state to the metallic state, which takes place at a critical temperature of about 68 °C. Much study has been especially devoted to developing advanced fabrication methodologies to improve the performance of VO2 thin films for phase-change applications in optical devices. Films structural and morphological characterisation is normally performed with expensive and time consuming equipment, as x-ray diffractometers, electron microscopes and atomic force microscopes. Here we propose a purely optical approach which combines Polarized Raman Mapping and Phase-Transition by Continuous Wave Optical Excitation (PTCWE) to acquire through two simple measurements structural, morphological and thermal behaviour information on polycrystalline VO2 thin films. The combination of the two techniques allows to reconstruct a complete picture of the properties of the films in a fast and effective manner, and also to unveil an interesting stepped appearance of the hysteresis cycles probably induced by the progressive stabilization of rutile metallic domains embedded in the semiconducting monoclinic matrix.

Abstract Chirality, the lack of mirror symmetry, can be mimicked in nanophotonics and plasmonics by breaking the symmetry in light-nanostructure interaction. Here we report on versatile use of nanosphere lithography for the fabrication of low-cost metasurfaces, which exhibit broadband handedness- and angle-dependent extinction in the near-infrared range, thus offering extrinsic chiro-optical behavior. We measure wavelength and angle dependence of the extinction for four samples. Two samples are made of polystyrene nanospheres asymmetrically covered by silver and gold in one case and silver only in the other case, with a nanohole array at the bottom. The other two samples are nanohole arrays, obtained after the nanosphere removal from the first two samples. Rich extrinsic chiral features are governed by different chiro-optical mechanisms in the three-dimensional plasmonic semi-shells and planar nanohole arrays. We also measure Stokes parameters in the same wavelength and incidence angle range and show that the transmitted fields follow the extrinsic chirality features of the extinction dissymmetry. We further study the influences of the nanostructured shapes and in-plane orientations on the intrinsic vs extrinsic chirality. The nanoholes are modelled as oval shapes in metal, showing good agreement with the experiments. We thus confirm that nanosphere lithography can provide different geometries for chiral light manipulation at the nanoscale, with the possibility to extend functionalities with optimized oval shapes and combination of constituent metals.

Abstract The COVID-19 pandemic caused by SARS-CoV-2 has highlighted the urgent need for innovative antiviral strategies to fight viral infections. Although a substantial part of the overall effort has been directed at the Spike protein to create an effective global vaccination strategy, other proteins have also been examined and identified as possible therapeutic targets. Among them, although initially underestimated, there is the SARS-CoV-2 E-protein, which turned out to be a key factor in viral pathogenesis due to its role in virus budding, assembly and spreading. The C-terminus of E-protein contains a PDZ-binding motif (PBM) that plays a key role in SARS-CoV-2 virulence as it is recognized and bound by the PDZ2 domain of the human tight junction protein ZO-1. The binding between the PDZ2 domain of ZO-1 and the C-terminal portion of SARS-CoV-2 E-protein has been extensively characterized. Our results prompted us to develop a possible adjuvant therapeutic strategy aimed at slowing down or inhibiting virus-mediated pathogenesis. Such innovation consists in the design and synthesis of externally PDZ2-ZO1 functionalized PLGA-based nanoparticles to be used as intracellular decoy. Contrary to conventional strategies, this innovative approach aims to capitalize on the E protein-PDZ2 interaction to prevent virus assembly and replication. In fact, the conjugation of the PDZ2 domain to polymeric nanoparticles increases the affinity toward the E protein effectively creating a “molecular sponge” able to sequester E proteins within the intracellular environment of infected cells. Our in vitro studies on selected cellular models, show that these nanodevices significantly reduce SARS-CoV-2-mediated virulence, emphasizing the importance of exploiting viral-host interactions for therapeutic benefit.

Adolescence is a crucial period for physical and psychological development. The impact of negative life events represents a risk factor for the onset of neuropsychiatric disorders. This study aims to investigate the relationship between negative life events and structural brain connectivity, considering both graph theory and connectivity strength. A group (n = 487) of adolescents from the IMAGEN Consortium was divided into Low and High Stress groups. Brain networks were extracted at an individual level, based on morphological similarity between grey matter regions with regions defined using an atlas-based region of interest (ROI) approach. Between-group comparisons were performed with global and local graph theory measures in a range of sparsity levels. The analysis was also performed in a larger sample of adolescents (n = 976) to examine linear correlations between stress level and network measures. Connectivity strength differences were investigated with network-based statistics. Negative life events were not found to be a factor influencing global network measures at any sparsity level. At local network level, between-group differences were found in centrality measures of the left somato-motor network (a decrease of betweenness centrality was seen at sparsity 5%), of the bilateral central visual and the left dorsal attention network (increase of degree at sparsity 10% at sparsity 30% respectively). Network-based statistics analysis showed an increase in connectivity strength in the High stress group in edges connecting the dorsal attention, limbic and salience networks. This study suggests negative life events alone do not alter structural connectivity globally, but they are associated to connectivity properties in areas involved in emotion and attention.

BACKGROUND: Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain injury and psychological distress after mild TBI using multimodal magnetic resonance imaging. METHODS: A total of 89 patients with mild TBI from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress approximately 6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. Magnetic resonance imaging data were acquired within 2 weeks after injury. Perivascular spaces (PVSs) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in FreeSurfer; diffusion imaging indices and multifiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates. RESULTS: PVS fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal-opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization. CONCLUSIONS: This study shows how PVS, cortical, and microstructural changes can predict the onset of depression, anxiety, and somatization symptoms in patients with mild TBI.

BackgroundPerivascular spaces (PVS) are fluid-filled spaces surrounding the brain parenchymal vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer’s disease (AD). The aim of this study is to investigate whether the relationship between MRI-visible PVS and stress is influenced by neuroinflammation in an elderly population with different levels of cognitive impairment.MethodsUsing brain MRI scans acquired at 1.5 T, PVS were quantified in a cohort of 461 individuals, consisting of cognitively healthy controls (n = 48), people with mild cognitive impairment (MCI, n = 322) and Alzheimer’s disease (AD, n = 91). PVS volume fraction was calculated in the basal ganglia and centrum semiovale using a semi-automated segmentation approach. Stress was quantified with levels of salivary cortisol. Inflammatory biomarkers measured from plasma included cytokines, matrix metalloproteinases and C-reactive protein. General linear models were used to test the relationship between PVS and cortisol, when interacting with inflammatory markers. This was done on the whole cohort and within each clinical cognitive group.ResultsIn the centrum semiovale, higher inflammation levels reduced the relationship of cortisol with PVS. In basal ganglia, higher levels of C-reactive protein reduced the negative relationship of cortisol with PVS. All analyses were accounted for age, sex, body mass index (BMI) and total hippocampal volume. There was a significant interaction effect between cortisol and C-reactive protein on PVS volume fraction in the MCI group.DiscussionThese findings suggest an influence of neuroinflammation on the PVS structure in Alzheimer’s disease spectrum, and offer insight for better understanding physiological processes of cognitive impairment onset.

Lung cancer represents the second most frequent neoplasm and the leading cause of neoplastic death among both women and men, causing almost 25% of all cancer deaths. Patients undergoing lung resection—both for primary and secondary tumors—require careful preoperative cardiopulmonary functional evaluation to confirm the safety of the planned resection, to assess the maximum tolerable volume of resection or to exclude surgery, thus shifting the therapeutic approach toward less invasive options. Cardiopulmonary reserve, pulmonary lung function and mechanical respiratory function represent the cornerstones of preoperative assessment of patients undergoing major lung resection. Spirometry with carbon monoxide diffusing capacity, split function tests, exercise tests and cardiologic evaluation are the gold standard instruments to safely assess the entire cardiorespiratory function before pulmonary resection. Although pulmonary mechanical and parenchymal function, together with cardiorespiratory compliance represent the mainstay of preoperative evaluation in thoracic surgery, the variables that are responsible for fitness in patients who have undergone lung resection have expanded and are being continually investigated. Nevertheless, because of the shift to older patients who undergo lung resection, a global approach is required, taking into consideration variables like frailty status and likelihood of postoperative functional deterioration. Finally, the decision to go ahead with surgery in fragile patients being consideredfor lung resection should be evaluated in a multispecialty preoperative discussion to provide a personalized risk stratification. The aim of this review is to focus on preoperative evaluation of cardiopulmonary reserve and surgical risk stratification of patients candidate for lung cancer resection. It does so by a literature search of clinical guidelines, expert consensus statements, meta-analyses, clinical recommendations, book chapters and randomized trials (1980–2022).

Rheumatoid arthritis (RA) is an autoimmune disease characterised by persistent inflammation of the synovial joints as well as other tissues and organs. Left untreated, it can lead to joint damage, disability and even increased mortality. The disease is driven by inflammatory cytokines that contribute to the chronic inflammation seen in RA. Interleukin-6 (IL-6) is a key pathological cytokine and a target for treatments aiming to alleviate local and systemic inflammation. Despite advances in understanding RA and the introduction of new treatments, achieving sustained remission remains challenging. This review explores the role of IL-6 in RA pathogenesis, its potential as a treatment target and the significance of personalised medicine in RA management. IL-6 has a dual signalling mechanism, classical and trans-signalling, which influences various intracellular pathways. While several targeted therapies have emerged, no single mechanism-based therapy is universally effective due to the diversity and complexity of the disease. Different approaches to targeting IL-6 have been tested, including biologic blockade of receptors or ligands, and inhibition of IL-6 signalling. IL-6 receptor inhibitors have been validated as RA therapeutics, either alone or in combination with other treatments. Tocilizumab, the first approved IL-6 inhibitor, blocks both soluble and membrane-bound IL-6 receptors, reducing the inflammatory cascade. Clinical trials confirm the efficacy and safety of tocilizumab and its role as a treatment option for patients unresponsive to conventional therapies. The benefits of IL-6 inhibition extend beyond reduced joint inflammation to the amelioration of comorbidities like anaemia, cardiovascular disease, depression and osteoporosis. Tailoring treatment to patients’ profiles and comorbidities is essential for optimal outcomes. A ‘treat-to-profile’ approach, focusing on a holistic view of the patient, could improve personalised medicine strategies. Biosimilars – lower-cost alternatives to biologics – further enhance the accessibility and cost-effectiveness of treatment. IL-6 inhibitors present a valuable treatment option for RA management, particularly for patients with specific comorbidities.

Introduction The therapeutic interest of targeting B-cell activating factor (BAFF) in Sjögren’s disease (SjD) can be suspected from the results of two phase II clinical trials but has not been evaluated in an animal model of the disease. We aimed to evaluate the therapeutic efficacy of this strategy on dryness and salivary gland (SG) infiltrates in the NOD mouse model of SjD.Material and methods Female NOD mice between ages 10 and 18 weeks were treated with a BAFF-blocking monoclonal antibody, Sandy-2 or an isotype control. Dryness was measured by the stimulated salivary flow. Salivary lymphocytic infiltrates were assessed by immunohistochemistry. Blood, SGs, spleen and lymph-node lymphocyte subpopulations were analysed by flow cytometry. SG mRNA expression was analysed by transcriptomic analysis.Results BAFF inhibition significantly decreased SG lymphocytic infiltrates, which was inversely correlated with salivary flow. The treatment markedly decreased B-cell number in SGs, blood, lymph nodes and spleen and increased Foxp3+ regulatory and CD3+CD4−CD8− double negative T-cell numbers in SGs.Conclusion A monoclonal antibody blocking BAFF and depleting B cells had therapeutic effectiveness in the NOD mouse model of SjD. The increase in regulatory T-lymphocyte populations might underlie the efficacy of this treatment.

Summary: Dendritic cell (DC) progenitors adapt their transcriptional program during development, generating different subsets. How chromatin modifications modulate these processes is unclear. Here, we investigate the impact of histone deacetylation on DCs by genetically deleting histone deacetylase 1 (HDAC1) or HDAC2 in hematopoietic progenitors and CD11c-expressing cells. While HDAC2 is not critical for DC development, HDAC1 deletion impairs pro-pDC and mature pDC generation and affects ESAM+cDC2 differentiation from tDCs and pre-cDC2s, whereas cDC1s are unchanged. HDAC1 knockdown in human hematopoietic cells also impairs cDC2 development, highlighting its crucial role across species. Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility, and histone acetylation of the transcription factors IRF4, IRF8, and SPIB required for efficient development of cDC2 subsets. Without HDAC1, DCs switch immunologically, enhancing tumor surveillance through increased cDC1 maturation and interleukin-12 production, driving T helper 1-mediated immunity and CD8+ T cell recruitment. Our study reveals the importance of histone acetylation in DC development and anti-tumor immunity, suggesting DC-targeted therapeutic strategies for immuno-oncology.

El propósito del artículo es presentar lo que podríamos llamar la “teoría de la temporalidad” de Spinoza en los Principios de filosofía de Descartes y su Apéndice, los Pensamientos metafísicos, publicados en 1663. Nuestro objetivo específico es determinar la naturaleza de la distinción precisa que se opera en esos escritos entre los conceptos de eternidad, duración y tiempo. Consideramos que con ello puede echarse luz no sólo a la forma en que evoluciona la doctrina de Spinoza, sino también comprender la distancia progresiva que nuestro autor toma respecto de la filosofía de Descartes en general, y de su ontología de la creación continua en particular.

The infiltration of immune cells into tissues underlies the establishment of tissue-resident macrophages and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here, we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio, which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect. In vivo imaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.

Background: Major thoracic trauma represents a life-threatening condition, requiring a prompt multidisciplinary approach and appropriate pathways for effective recovery. While acute morbidity and mortality are well-known outcomes in thoracic-traumatized patients, long-term quality of life in patients surviving surgical treatment has not been widely investigated before. Methods: Between November 2016 and November 2023, thirty-two consecutive patients were operated on because of thoracic trauma. Age, sex, comorbidities, location and extent of thoracic trauma, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), Organ Injury Scale (OIS), intra and extrathoracic organ involvement, mechanism of injury, type of surgical procedure, postoperative complications, ICU and total length of stay, immediate clinical outcomes and long-term quality of life—by using the EQ-5D-3L scale and Numeric Rate Pain Score (NPRS)—were collected for each patient Results: Results indicated no significant difference in EQOL.5D3L among patients with thoracic trauma based on AIS (p = 0.55), but a significant difference was observed in relation to ISS (p = 0.000011). Conclusions: ISS is correlated with the EQOL.5D3L questionnaire on long-term quality of life, representing the best prognostic factor—in terms of long-term quality of life—in patients surviving major thoracic trauma surgical treatment.

The article ‘EGFR/Ras-induced CCL20 production modulates the tumour microenvironment’, written by Andreas Hippe, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber, Anne Schorr, Stephan Seeliger, Stephanie Holtz, Katharina Jannasch, Andor Pivarcsi, Bettina Buhren, Holger Schrumpf, Andreas Kislat, Erich Bünemann, Martin Steinhoff, Jens Fischer, Sérgio A. Lira, Petra Boukamp, Peter Hevezi, Nikolas Hendrik Stoecklein, Thomas Hoffmann, Frauke Alves, Jonathan Sleeman, Thomas Bauer, Jörg Klufa, Nicole Amberg, Maria Sibilia, Albert Zlotnik, Anja Müller- Homey and Bernhard Homey, was originally published electronically on the publisher’s internet portal on 30 June 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 16 September 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. Open Access funding enabled and organized by Projekt DEAL.

The active modulation of optical response of quantum emitters at the nanoscale is of paramount importance to realize tunable light sources for nanophotonic devices. Herein, a thin film of phase‐change material (VO2) is coupled to a 20 nm‐thick silica layer embedding Er3+ ions, and it is demonstrated how the active tuning of the local density of optical states near the erbium emitters provided by the thermally induced semiconductor‐to‐metal transition of VO2 can be used to dynamically control the Er3+ emission lifetime at telecom wavelength (1.54 μm). A decay rate contrast of a factor 2 is obtained between high temperature (90 °C), when VO2 is metallic, and room temperature, when VO2 is semiconductor, in agreement with calculations performed with the classical dipole oscillator analytical model. A hysteretic behavior is observed by measuring the Er3+ lifetime as a function of the temperature, whose parameters are consistent with those of grazing incidence X‐ray diffraction and optical transmittance measurements. The fractions of Er3+ ions that couple with VO2 in each phase at the different temperatures are determined by the analysis of the temporal decays. The results make the investigated system an optimal candidate for the development of tunable photon sources at telecom wavelength.

ObjectiveThis study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).MethodsWe retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.ResultsOf 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (

Abstract FAM3C/ILEI is an important cytokine for tumor progression and metastasis. However, its involvement in inflammation remains elusive. Here, we show that ILEI protein is highly expressed in psoriatic lesions. Inducible keratinocyte‐specific ILEI overexpression in mice (K5‐ILEIind) recapitulates many aspects of psoriasis following TPA challenge, primarily manifested by impaired epidermal differentiation and increased neutrophil recruitment. Mechanistically, ILEI triggers Erk and Akt signaling, which then activates STAT3 via Ser727 phosphorylation. Keratinocyte‐specific ILEI deletion ameliorates TPA‐induced skin inflammation. A transcriptomic ILEI signature obtained from the K5‐ILEIind model shows enrichment in several signaling pathways also found in psoriasis and identifies urokinase as a targetable enzyme to counteract ILEI activity. Pharmacological inhibition of urokinase in TPA‐induced K5‐ILEIind mice results in significant improvement of psoriasiform symptoms by reducing ILEI secretion. The ILEI signature distinguishes psoriasis from healthy skin with uPA ranking among the top “separator” genes. Our study identifies ILEI as a key driver in psoriasis, indicates the relevance of ILEI‐regulated genes for disease manifestation, and shows the clinical impact of ILEI and urokinase as novel potential therapeutic targets in psoriasis.

The temperature tunability of complex dielectric constants of vanadium dioxide (VO2) makes it a promising phase-change material for use in active, dynamic, tunable photonics applications. Specifically, the semiconductor-to-metal phase transition in VO2 enables reversible, broadband, and large complex refractive index variation and paves the way for a plethora of applications. Although the critical temperature for phase-transition is 68 °C for VO2 films, its transition temperature can be reduced to room temperature by tungsten-doping of vanadium dioxide. Such a degree of freedom in controlling the critical temperature through tungsten doping provides further tunability of the thermochromic behavior. In this work, we investigate a variety of W-doped VO2 thin films deposited by laser ablation of targets with increasing W doping content and report detailed infrared characterization together with numerical simulations. Our experimental results indicate that the perfect absorption can be achieved at different temperatures, within the VO2 insulator-to-metal phase transition process, as a function of W doping content. Tunable subwavelength layers allow perfect absorption under different temperature conditions around λ = 12 µm. We show that a high dynamic range of reflectivity can be achieved when the temperature is increased above the phase transition temperature. Furthermore, we observe perfect absorption at 11.8 µm at room temperature for a W content of 0.75%. We believe that W-doped VO2 thin films with tunable and controllable perfect absorption will open the way for a class of promising thermo-optical devices including thermos-photovoltaics, infrared filters, radiative cooling devices, and thermal emitters.

BackgroundThe activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.MethodsThe effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.ResultsTumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.ConclusionWe propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.