Susetta Finotto

Long-term nourishment with quercetin, a naturally occurring plant flavonoid abundant in citrus fruits, buckwheat, and onions, has been associated with reduced risks of chronic diseases, including cancer. In this study, we evaluated the therapeutic potential and the anti-cancer properties of quercetin in lung cancer using in vitro, in vivo, and ex vivo models. Quercetin induced tumor cell cycle arrest via the p53-p21 axis and suppressed tumor cell migration in both the A549 and H520 human lung cancer cell lines. Moreover, it reduced oxidative stress and downregulated the protein expression of oncogenic markers such as EGFR and PD-L1 on the surface of A549 cells in a dose-response manner. Quercetin significantly attenuated the proliferation and migration of the tumor cells. In an in vivo model, quercetin decreased the tumor load without affecting the body weight. In the ex vivo model, quercetin treatment resulted in the induction of interferon alpha-2 (IFN-α2), a well-known anti-tumor cytokine. These findings demonstrate that quercetin exerts potent anti-tumoral and anti- inflammatory effects in lung cancer by regulating cell cycle, oxidative stress, and immune pathways.

Background: Lung cancer is the leading cause of cancer-related death in the world. Blimp-1 is a transcriptional repressor that, by interacting with other transcription factors in lymphocytes, regulates their cellular fate. Objective: In this study, we focused on the role of Blimp-1 in T cells in lung cancer. Methods: Here, we analyzed, in a murine model of NSCLC, the role of Blimp-1 in T cells after targeting Blimp-1 in T cells expressing lymphocyte-specific-protein tyrosine kinase (Lck), a kinase crucial for T-cell receptor signaling. Results: We found that mice lacking Blimp1 expression in T cells have reduced lung tumor load, suppressed lung Foxp3+Treg cells in the lung and draining lymph nodes, and induced T-bet+CD4+T effector cells producing IFN-gamma and interleukin-2. Furthermore, RNA sequencing of spleen CD4+T cells showed an induction of Th1 markers, including TNF, IL-2 and interferon type I-related genes, but also PD1. RNA sequencing of spleen CD8+T cells showed induced Tc1 markers, including IL12rb1, CD44, granzyme M and eomesodermin, in the absence of Blimp1. Finally, in the lung of mice with Blimp1 deficiency in T cells, we found an upregulation of CD8+T cells with increased release of cytotoxic mediators able to induce lung tumor cell death. Conclusions: These data indicate that the tumor microenvironment induces Blimp-1 in immunosuppressive Treg and T effector cells, thereby limiting the therapeutic efficacy of anti-tumor immune responses. Targeting of Blimp-1 in T cells emerges as a novel concept to suppress immune evasion in lung cancer by regulating CD4+, CD8+and Treg function in the lung.

Human rhinovirus (HRV) is one of the common respiratory viral infection agents that triggers airway obstruction and asthma exacerbations, especially during childhood. This project aimed at evaluating the mechanism of ultraviolet (UV) and infrared (IR) radiations to inactivate HRV infection and replication inside and outside infected airway epithelial cells and the resulting impact on interferon responses and epithelial barrier integrity. Hereby, airway epithelial cells were infected with different RV concentrations. Later these cells are exposed to UV and IR light to analyze their impact on the viral immune response of the host by real-time PCR. It was found that RV1B disrupted cell junctions of airway epithelial cell barriers. Moreover, high doses of RV1B activated pattern recognition receptor (TLR3), induced interferon (IFN-β) response and reduced SOCS1, which is a negative regulator of IFN-β. Further, IR lights inhibited rhinovirus post infection in primary nasal epithelial cells (NECs). Finally, UVC exposure significantly inhibited the antiviral effects of the host via SOCS1 inhibition and decreased RV1B within 72 h. Collectively, these findings support the role of UV light as an effective therapeutic approach for acutely eliminating RV but resulting in barrier and antiviral damage, which can have a drawback effect for asthma.

Air pollution has been recognised as the single biggest environmental threat to human health within the European Union (EU). Indoor air pollution has received less attention than outdoor air pollution, even though we spend most of our time indoors. It is associated with a variety of short‐ and long‐term health effects. These include allergies and asthma with a key role for the exposure to bioaerosols and synergistic interactions between chemical and biological pollutants. Given the dramatic rise of allergic diseases, the prevention of symptom exacerbations and the new onset of disease are of great importance, particularly for vulnerable populations such as children. The lack of a unified EU‐wide approach involving all stakeholders represents a major unmet need. The EU‐funded IDEAL Cluster comprises seven research projects to advance knowledge on indoor air quality (IAQ) and its impact on health, inform policies and thus promote healthier indoor environments. The ‘SynAir‐G’ project forms part of this cluster and was launched in 2022 with the participation of 18 partners from 11 countries. It focuses on schools to explore synergistic interactions between chemical and biological pollutants based on the hypothesis that these modulate major health effects. SynAir‐G includes the development of low‐cost sensors, collection of health outcomes, modelling of pollution dynamics and the development of mitigation solutions. The knowledge will be circulated to all stakeholders and the public aiming to establish standards and health‐based guidelines. The scope of this position statement is (1) to review the current evidence on indoor air pollution, its impact on health and particularly on children with allergies and asthma; (2) to give an overview of the European regulatory framework; (3) to describe knowledge gaps, challenges and unmet needs; and (4) to present SynAir‐G′s project goals and propose a roadmap to improve IAQ for children with asthma and allergies.

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality, and most patients fail to respond to immune checkpoint inhibitors (ICIs). Nutritional factors, particularly dietary lipids, influence cancer progression and immunity. Cholesterol can promote tumor growth and immune evasion, whereas ω−3 polyunsaturated fatty acids (PUFAs) may exert anti-inflammatory and immunostimulatory effects. We aimed to determine how dietary lipids influence NSCLC progression and whether ω−3 PUFA supplementation can enhance the efficacy of PD-1 blockade. Methods: Serum lipid profiles from 152 NSCLC patients were analyzed for associations with prognosis. Female murine NSCLC models were fed diets enriched in cholesterol, saturated fats, or ω−3 PUFAs, with or without anti-PD-1 therapy. Tumor growth, immune infiltration, cytokine production, and epithelial–mesenchymal transition (EMT) markers were assessed by flow cytometry, ELISA, and gene expression analysis. Results: In patients, elevated serum triglycerides correlate with poor outcomes, and tumor cholesterol metabolism links to EMT marker expression. In female mice, cholesterol-rich diets accelerate tumor growth, increase EMT-associated genes (SNAIL, Vimentin), and elevate pro-tumoral cytokines (IL-6, IL-10, IL-17A). ω−3 PUFA diets reduce tumor burden, lower immunosuppressive cytokines, decrease regulatory T cells, and enhance cytotoxic T cell activity. Combining ω−3 PUFAs with anti-PD-1 therapy synergistically suppresses tumor growth and improves antitumor immune responses. Conclusions: Dietary lipids modulate NSCLC progression via metabolic, inflammatory, and immune pathways. ω−3 PUFA supplementation counteracts cholesterol-driven tumor promotion and augments PD-1 blockade efficacy, supporting dietary modulation as a complementary strategy to improve immunotherapy outcomes in NSCLC.

Background: Immune checkpoint inhibitors targeting the interaction between PD1 and PDL1 are effective for immunotherapy in non-small cell lung cancer (NSCLC). However, only subgroups of patients respond to therapy, suggesting the existence of resistance mechanisms. Methods: In this study, we analyzed post-surgery lung tissues and peripheral blood cells from patients with Non Small Cell Lung Cancer (NSCLC) and control subjects by using western blot, immunohistochemistry, ELISA, multiplex cytokine, and qPCR analysis. Results: Here, we found progressively increased Blimp1 expression in the tumoral region of NSCLC patients, where Slamf1 significantly decreased, and it inversely correlated with Blimp1. In PBMCs, Blimp1 was expressed in CD8+ T cells but predominantly in immunosuppressive Foxp3+ Treg cells or after targeting of the T cell activator Slamf1. Anti-CD3/CD28 induced IL-6 and IL-10, an immunosuppressive gene induced by Blimp1, in the supernatants of PBMCs from patients with NSCLC. Targeting PD1 in PBMCs reduced Blimp1. Conclusions: Here, we identify a key role of the transcription factor Blimp1 for immune evasion in NSCLC. Thus, targeting Blimp1 emerges as a novel concept to improve current lung cancer immunotherapies and to suppress immune evasion in lung cancer.

Background and objective: Particulate matters such as diesel exhaust particles induce oxidative stress in cells and thereby have a negative impact on health. The aim of this study was to test whether the membrane-permeable, anti-inflammatory metabolite 4-Octyl Itaconate can counteract the oxidative stress induced by diesel exhaust particles and to analyze the downstream-regulated pathways both in human nasal epithelial cells and PBMCs.Methods: Human nasal epithelial cells were cultured from nasal swabs, and the response of the cells to diesel exhaust particles either alone or in combination with 4-Octyl Itaconatee was investigated using RNA sequencing, qPCR, and cytokine measurement. The presence of reactive oxygen species in the cells was analyzed using CellROX staining and flow cytometric DCFDA assay.Results: Diesel exhaust particles caused an upregulation of CYP1A1 in nasal epithelial cells. The administration of 4-Octyl Itaconate reduced the reactive oxygen species and increased the expression of antioxidant genes regulated by the transcription factor NRF2, which was also confirmed in PBMCs. IL-6 secretion from NEC was elevated by diesel exhaust particles and reduced when 4-Octyl Itaconate was administered.Conclusion: 4-Octyl Itaconate can reduce the diesel-exhaust-particle-induced oxidative damage by the activation of NRF2-regulated antioxidative pathways.

Background: Lung cancer is one of the most common types of cancer, which can currently be cured only partially. Even though the function of the transcription factor PU.1 as an oncogene has already been investigated in detail in various studies, its precise function and regulatory mechanisms in non-small cell lung cancer (NSCLC) remain to be fully elucidated.Methods: Patients with NSCLC and healthy controls were recruited at the Department of Thoracic Surgery of the University Hospital Erlangen. Tissue samples were dissected from patients who underwent lung tumor surgery and blood samples were collected from all participants.Results: In this study, we showed that the expression of PU.1 was increased both in the blood and in the tumor region of the lung of patients with NSCLC. On a more detailed analysis, PU.1 was found increased the most in CD56^dim natural killer cells (NK cells). Furthermore, we demonstrated an increased cytotoxic potential for PU.1 expressing cells as well as improved overall and recurrence-free survival for patients with a higher expression of PU.1, suggesting a beneficial role for PU.1 in NSCLC.Conclusion: High expression of PU.1 associated with NK cells could lead to a beneficial outcome and survival of NSCLC patients.

Understanding the dynamic pathophysiology of diseases in the lung, such as asthma and chronic asthma, chronic obstructive pulmonary disease, and lung cancer, is crucial for the treatment, analysis, and outcome of these diseases. Unlike other traditional models, we suggest a protocol that is sustainable and reproducible and offers different analysis methods while maintaining in vivo lung architecture and immune dynamics. This protocol allows one to study the pathophysiological changes, including changes to the immune cells, cytokines, and mediators, in 30 precision‐cut lung slices from a single murine lung. To accomplish this, the murine lung is infused with 2.5% low‐melting‐point agarose and is precision‐cut‐sliced. Our method also supports cell culture in refined medium and stimulation with clinically relevant stimuli, which helps to clarify the mechanisms of the disease. Evaluation of the samples and their supernatant includes multiplex assays, ELISA, histology, and immunohistochemistry. Additional sections are used to extract RNA for quantitative real‐time PCR and RNA sequencing and/or other selected analysis, like flow cytometry. Using this method, we obtained murine lung slices that preserve the pathophysiology of the disease and allow a comprehensive analysis unlike other already‐existing protocols. By retaining the dynamic immune mechanisms, we are able to see the histological damage caused by each disease. The results of this protocol can be used to improve our understanding and therapy options. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol: Obtaining precision‐cut lung slices (PCLSs) from the murine lungSupport Protocol 1: LL/2 cell treatment with G‐418 solutionSupport Protocol 2: Murine model of lung adenocarcinoma and in vivo imagingSupport Protocol 3: H&E staining of PCLS sectionsSupport Protocol 4: Measuring cytokines by ELISASupport Protocol 5: Measuring cytotoxic activity in PCLS conditioned mediumSupport Protocol 6: Analysis of RNA from PCLSs by real‐time PCRSupport Protocol 7: Flow cytometry analysis of cells isolated from PCLSs