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Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T (Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE. Systemic Lupus Erythematosus (SLE) is a chronic and progressive autoimmune disease characterized by abnormally activated B cells causing organ damage. Here authors introduce an adoptive cell therapy involving regulatory T cells overexpressing FoxP3 and harboring an anti-CD19 CAR to inhibit pathological B cells and thus tissue-harming autoimmunity in a humanized mouse model.

A bstract Electromagnetic corrections to hadronic vacuum polarization contribute significantly to the uncertainty of the Standard Model prediction of the muon anomaly, which poses conceptual and numerical challenges for ab initio lattice determinations. In this study, we compute the non-singlet contribution from intermediate Euclidean current separations in quantum chromo- and electrodynamics (QCD+QED) using C ⋆ boundary conditions in two ways: either non-perturbatively by sampling the joint probability distribution directly or by perturbatively expanding from an isospin-symmetric theory. This allows us to compare the predictions and their uncertainties at a fixed lattice spacing and volume, including fully the sea quarks effects in both cases. Treating carefully the uncertainty due to tuning to the same renormalized theory with N f = 1 + 2 + 1 quarks, albeit with unphysical masses, we find it advantageous to simulate the full QCD+QED distribution given a fixed number of samples. This study lays the ground-work for further applications of C ⋆ boundary conditions to study QCD+QED at the physical point, essential for the next generation of precision tests of the Standard Model.

A retrospective case-control study was carried out on 80 patients with sporadic frontotemporal dementia and 124 age, sex, and surrogate informant matched controls with respect to various medical and environmental risk factors. Head trauma was associated with an odds ratio of 3.3 (95% confidence interval (CI), 1.3 to 8.1). Although recall bias may play a role, the frontal lobes are known to be especially vulnerable to even mild head trauma. Thyroid disease was associated with a 2.5 times increased risk of frontotemporal dementia (95% CI, 0.9 to 7.9), which was not statistically significant (p = 0.09) owing to limited power. As altered thyroid hormone status has been observed before in frontotemporal dementia, future studies will be important to confirm this observation.

Abstract OP 32: Health Status 1, B210 (FCSH), September 5, 2025, 09:00 - 10:00 Aim: The WHO Action Plan for Refugee and Migrant Health highlights the need for strengthened migration health governance and data-driven policymaking. However, the absence of systematically collected and comparable health data among migrants remains a critical barrier. Approximately 12% of the European population (87 million people) has a migration background, and the risk of cancer among migrants can differ significantly from both their country of birth and their host country. Cancer RADAR aims to address this knowledge gap by providing a Europe-wide quantification of infection-related and screening-detectable cancer risks, stratified by migration background. We present the feasibility of such systematic data collection. Methods: Cancer RADAR explores the feasibility and methodology of mapping infection-related (liver, stomach, and cervical) and screening-detectable (cervical, breast, colorectal, and lung) cancer risks among individuals with a migration background across Europe. In collaboration with pilot cancer registries, we co-created a protocol to systematically collect cancer data stratified by birth country, serving as a proxy for first-generation migration background. Results: Cancer data stratified by birth country is available from 44 cancer registries and through data linkage from 8 cancer registries representing 20 European countries. Barriers to data collection include time constraints, limited infrastructure, financial resources, and the need for ethical approvals in the case of data linkage. Facilitators include the opportunity to contribute to decreasing inequalities in cancer outcomes and increase the visibility of a registry. Data from pilot cancer registries confirm increased risks for infection-related cancers and a similar or decreased risks for colon and breast cancer among individuals with a migration background, compared to the host population. Conclusion: We present the feasibility of quantifying and monitoring cancer risks among migrants, with the goal to provide actionable evidence to inform data-driven policymaking aimed at reducing health disparities.

•High breast density was inversely associated with grade.•No associations with hormonal tumour characteristics were observed.•Breast adipose cells may support an environment favourable to higher grade tumours. Inconclusive data exist on the association between breast density and breast cancer characteristics. We conducted a case-only study on 667 invasive breast cancers, using data from the Piedmont Cancer Registry. We applied a multivariate logistic regression model to estimate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of high breast density (Breast Imaging Reporting and Data System, BI-RADS 3−4) versus low (BI-RADS 1−2) in relation to histologic grade, pathological tumour size and lymph node status, histotype, estrogen and progesterone receptor, HER2 and Ki67 status. Histopathological data were assessed according to the American Joint Committee on Cancer (AJCC) Staging Manual guidelines. The model includes terms for age at diagnosis, education level, body mass index, reproductive factors, family history of breast cancer, smoking and diabetes. As regards histologic grade, compared to well differentiated tumours, the OR of high (versus low) breast density cases was 0.61 (95% CI 0.38−0.98) for moderately-poorly differentiated tumours. No other associations with hormonal and histopathological characteristics were observed. Our results indicate that low breast density is associated with moderately-poorly differentiated breast tumours.

ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

BackgroundSystemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an abnormal inflammatory response against nuclear antigens with consequent tissue damage. Autoreactive B cells and auto-antibodies have a fundamental role in SLE pathogenesis. Regulatory T cells (Tregs) physiologically maintain the immune tolerance and are impaired in SLE. Polyclonal Treg trnasfer obtained unsatisfactory results due to the low number of disease-relevant antigen-specific cells. Chimeric Antigen Receptors (CARs) are molecules capable of redirecting T cell specificity. CAR-Tregs proved effective in pre-clinical mouse models of autoimmunity.ObjectivesWe aimed at developing a CAR-Treg based product to be employed in SLE.MethodsWe isolated Tregs from Healthy Donors Peripheral Blood Mononuclear Cells (PBMCs) and expanded them with IL-2 and rapamycin. We transduced Tregs with a Lentiviral Vector encoding for a second-generation anti-CD19 CAR, considering the relevant role of autoreactive B cells and autoantibodies in SLE.ResultsEngineered cells retained their immune suppressive capabilities upon polyclonal stimulation. Noticeably, they acquired new antigen-specific suppressive capacities, being able to block autologous B cell proliferation. We set up a humanized mouse model of SLE. In vivo, CAR-Tregs delayed the occurrence of B cell lymphopenia, producing immunomodulatory cytokines and without showing toxicity or reprogramming towards Th17 pro-inflammatory cells. In inflamed organs, CAR-Tregs restored the normal composition of the immune system.ConclusionIn conclusion, we efficiently generated anti-CD19 CAR-Tregs and proved their efficacy both in vitro and in an in vivo humanized mouse model of lupus.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case–case–control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR adj for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR adj 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR adj 2.6 for more than 7000 lifelong hours) and BCC (OR adj 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR adj 2.2 for more than 6000 lifelong hours). In the case–case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.