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Povzetek: Pharyngeal squamous cell carcinoma (PSCC) is a significant health concern, with human papillomavirus 16 (HPV16) playing a key role in the etiology of oropharyngeal squamous cell carcinoma (OPSCC). HPV16-related OPSCC exhibits enhanced radiosensitivity compared to HPV16-unrelated PSCC, yet the underlying mechanisms remain poorly understood. As HPV16 oncoproteins E6 and E7 are known to interfere with innate immune signaling, we investigated how modulation of cytosolic DNA sensing pathways and innate immune responses changes after irradiation (IR) and whether this contributes to enhanced radiosensitivity in HPV16-related OPSCC. Materials and methods Using HPV16-related and -unrelated PSCC models, we examined baseline expression levels of DNA sensors and cytokines and assessed the effects of IR on double-stranded DNA (dsDNA) accumulation, activation of cytosolic DNA sensors, cytokines, and immune cell infiltration both in vitro and in vivo. Analyses were performed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescent staining. Results HPV16-related OPSCC exhibited a distinct baseline expression profile of DNA sensors and cytokines, consistent with suppression of the stimulator of interferon genes (STING) pathway. While IR-induced activation of DNA sensors was dose- and time-dependent across models, HPV16-related OPSCC showed selective activation of cyclic GMP-AMP synthase (cGAS) and STING without significant cytokine upregulation or immune activation. In contrast, HPV16-related and unrelated PSCCs displayed activation of multiple DNA sensors, increased cytokine expression, and enhanced immune cell infiltration following IR. Conclusions The key finding was that the involvement of cytosolic DNA sensing pathways and innate immune system do not increase radiosensitivity of HPV16-related OPSCC. In PSCC models, DNA sensor and cytokine expression varied depending on IR dose and fractionation.
Ključne besede: human papillomavirus, oropharyngeal squamous cell carcinoma, radiosensitivity
Objavljeno v DiRROS: 16.01.2026; Ogledov: 170; Prenosov: 60
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Povzetek: Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients’ lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field since 2018, marked by successful gene therapy trials and treatments for various rare diseases. Significant strides have been made in the field of gene therapy in Slovenia, treating patients with spinal muscular atrophy and rare metabolic disorders, including the pioneering work on CTNNB1 syndrome. Additionally, immune gene therapy, exemplified by IL-12 adjuvant therapy for cancer, has been a focus of research in Slovenia. Through patient-centred initiatives and international collaborations, researchers in Slovenia are advancing preclinical research and clinical trials, paving the way for accessible gene therapies. Establishing clinical infrastructure and genomic diagnostics for rare diseases is crucial for gene therapy implementation. Efforts in this regard in Slovenia, including the establishment of a Centre for Rare Diseases, Centre for the Technologies of Gene and Cell Therapy, and rapid genomic diagnostics, demonstrate a commitment to comprehensive patient care. Despite the promises of gene therapy, challenges remain, including cost, distribution, efficacy, and long-term safety. Collaborative efforts are essential to address these challenges and ensure equitable access to innovative therapies for patients with rare diseases.
Ključne besede: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Objavljeno v DiRROS: 04.12.2025; Ogledov: 360; Prenosov: 206
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Ključne besede: onkološki bolniki, melanom, multidisciplinarna obravnava
Objavljeno v DiRROS: 26.11.2025; Ogledov: 506; Prenosov: 129
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Ključne besede: glava, vrat, rak (medicina), oralni mukozitis, simptomi, preprečevanje, zdravljenje
Objavljeno v DiRROS: 08.08.2025; Ogledov: 396; Prenosov: 133
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Povzetek: Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 [n = 4] vs. 1.8% in grade 2 [n = 3] or no reaction [n = 1] at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab.
Ključne besede: alpha-gal, baseline serum tryptase, basophil activation test, cetuximab, drug allergy
Objavljeno v DiRROS: 22.07.2025; Ogledov: 836; Prenosov: 376
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