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Iskalni niz: "ključne besede" (immunotherapy) .

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1.
Immunophenotyping, activation, and expansion of gamma delta T cells: flow cytometry profiling and ex vivo manipulation strategies
Urška Rupar, Pia Bertoncelj, Katja Leben Zupet, Gašper Markelj, Tina Vesel, Neja Šamec, Tadej Avčin, Jelka Pohar, Anže Smole, 2026, izvirni znanstveni članek

Povzetek: Gamma delta (γδ) T cells exhibit unique antiviral, antibacterial, and antitumor properties. Advancing the fundamental understanding of γδ T cell immunobiology and unlocking their full therapeutic potential requires detailed immunophenotypic profiling alongside optimized strategies for ex vivo activation and expansion. In this review, we synthesize current knowledge of γδ T cell immunobiology, emphasizing (i) comprehensive phenotypic characterization using flow cytometry and (ii) emerging approaches for their therapeutic implementation, with a focus on activation and ex vivo expansion methods. By integrating insights from phenotypic analysis with a comparative evaluation of expansion techniques, we provide an overview of γδ T cell immunobiology and their translational potential in immunotherapy.
Ključne besede: barrier immunity, cellular immunotherapy, flow cytometry, gamma delta (γδ) T cells, immune dysregulation, immunophenotyping, γδ T cell activation, γδ T cell expansion, immunology
Objavljeno v DiRROS: 03.08.2026; Ogledov: 181; Prenosov: 99
.pdf Celotno besedilo (1,57 MB)
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2.
The influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukaemia
Tomaž Prelog, Simon Buček, Andreja Brožič, Jakob Peterlin, Marko Kavčič, Maša Omerzel, Boštjan Markelc, Tanja Jesenko, Veronika Kloboves-Prevodnik, 2024, izvirni znanstveni članek

Povzetek: Flow cytometry plays is important in the diagnosis of acute lymphoblastic leukaemia (ALL) and when antigen-specific immunotherapy is indicated. We have investigated the effects of prednisolone, vincristine, daunorubicin, asparaginase and methotrexate on the antigen expression on blast cells that could influence the planning of antigen-specific therapy as well as risk-based treatment assignment. Patients and methods. Patients aged ≤ 17 years with de novo B-cell ALL (B-ALL) were enrolled in the study. Blast cells were isolated and exposed in vitro to 5 individual cytotoxic drugs in logarithmically increasing concentrations. Then, the expression of CD10, CD19, CD20, CD27, CD34, CD45, CD58, CD66c and CD137 antigens was determined by quantitative flow cytometry. Results. Cytotoxic drugs caused dose-dependent or dose-independent modulation of antigen expression. Daunorubicin caused a dose-dependent down-modulation of CD10, CD19, CD34, CD45 and CD58 and an up-modulation of CD137. Vincristine caused a dose-dependent down-modulation of CD19 and CD58 and an up-modulation of CD45. Daunorubicin also caused dose-independent down-modulation of CD27 and prednisolone down-modulation of CD10, CD19, CD27, CD34 and CD58. Down-modulation of CD20 was detected only in relation to the specific dose of daunorubicin. Conclusions. The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.
Ključne besede: immunophenotypic changes, chemotherapy, immunotherapy
Objavljeno v DiRROS: 26.06.2026; Ogledov: 179; Prenosov: 95
.pdf Celotno besedilo (1,04 MB)

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Adjuvant nivolumab in resected oesophageal or gastroesophageal junction cancer following neoadjuvant chemoradiotherapy : Slovenian real-world data
Nežka Hribernik, Rozala Arko, Gorana Gašljević, Martina Reberšek, 2026, izvirni znanstveni članek

Povzetek: Adjuvant nivolumab has become the new standard of care for patients with oesophageal and gastroesophageal junction cancer (OEC/GEJC) following neoadjuvant chemoradiotherapy (neoCRT) and surgical resection. In Slovenia, this treatment has been in use since January 2022. Here, we report the first Slovenian real-world experience with adjuvant nivolumab. Patients and methods. We conducted a retrospective, observational cohort study of patients with OEC/GEJC who received adjuvant nivolumab after neoCRT and radical resection between January 2022 and December 2023. Data on patient characteristics, treatment completion, disease progression, and immune-related adverse events (irAEs) were collected from medical records and analysed via descriptive statistics. Results. A total of 17 patients were included. The median follow-up was 34.6 months (range 11.2–55.7). The cohort included 14 (82%) males, with a mean age of 59 years. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 15 (88%) patients and 1 for 2 (12%) patients. The tumor location was the esophagus in 9 (53%) patients and the gastroesophageal junction in 8 (47%) patients. At diagnosis, 13 (76%) patients were stage III (8th TNM classification). Histology revealed adenocarcinoma (AC) in 12 (71%) patients and squamous cell carcinoma (SCC) in 5 (29%) patients. Only 6 (35%) patients completed one year of adjuvant nivolumab. Treatment was discontinued in 5 (29%) patients due to disease progression and in 6 (35%) patients due to irAEs. Overall, 11 (65%) patients experienced irAEs of any grade. Grade 3 or 4 irAEs occurred in 4 (24%) patients: myocarditis G4 in 1 (6%) patient and colitis G3 in 3 (18%) patients. No irAE-related deaths were reported. The median disease-free survival (DFS) was 21.4 months (95% confidence interval [CI], 14.6–28.9). Conclusions. Real-world data from Slovenia indicate that 65% of patients discontinued adjuvant nivolumab prematurely due to disease progression or irAEs. These findings highlight the need for careful patient selection and monitoring when using adjuvant immunotherapy in this population.
Ključne besede: oesophageal cancer, gastroesophageal junction cancer, adjuvant immunotherapy, nivolumab
Objavljeno v DiRROS: 18.06.2026; Ogledov: 216; Prenosov: 89
.pdf Celotno besedilo (828,77 KB)

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Glioblastoma–natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axis
Anamarija Habič, Tina Kolenc Milavec, Pia Žižek, Špela Kladnik, Bernarda Majc, Emanuela Senjor, Milica Perišić, Andrej Porčnik, Borut Prestor, Urban Švajger, Metka Novak, Barbara Breznik Vittori, 2026, izvirni znanstveni članek

Povzetek: Glioblastoma (GB) is an aggressive primary brain cancer with poor patient prognosis. Natural killer (NK) cells can recognise and eliminate a range of malignant cells, including GB stem cells, which drive GB recurrence. NK cell-based immunotherapy has emerged as a promising approach for GB treatment, but a better understanding of the complex crosstalk between GB and NK cells is needed, particularly within the immunosuppressive GB tumour microenvironment. In this study, we established a reproducible protocol for the production and dynamic culture of uniformly sized GB spheroids using the Celvivo Clinostar system. Our spheroids recapitulated the heterogeneous structure of GB and expressed ligands for NK cell receptors at levels distinct from those observed in corresponding GB cell lines in standard culture, implicating altered sensitivity of GB cells to NK cells in dynamic 3D cultures. GB-NK cell crosstalk was GB cell type dependent and the ability of NK cells to infiltrate GB did not necessarily correlate with their cytotoxicity against GB cells. Spheroids derived from differentiated GB cells secreted higher levels of immunomodulatory cytokines compared to spheroids from GB stem-like cells, and a prominent increase in the secretion of immune-attracting factors was observed in their co-cultures with NK cells. Finally, the CD155-DNAM1/TIGIT axis was indicated as an important regulator of NK cell cytotoxicity against GB stem-like cells. Collectively, our results highlight important factors in GB-NK cell communication and provide a groundwork for further targeted research as well as therapeutic evaluation of NK cell-based approaches in the established dynamic 3D cultures.
Ključne besede: glioblastoma, immunotherapy, dynamic in vitro models, natural killer cells, cytotoxicity, 21 infiltration, cytokines, CD155
Objavljeno v DiRROS: 11.06.2026; Ogledov: 272; Prenosov: 233
.pdf Celotno besedilo (6,86 MB)
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The role of antibody-drug conjugates in the treatment of lung cancer
Tanya Zlatanova, Aynura Changalova, Urška Janžič, 2026, izvirni znanstveni članek

Povzetek: Over the last decades, lung cancer treatment has improved immensely, mainly due to the incorporation of new targeted treatments and immunotherapy. A relatively new and potentially highly effective class of drugs, antibody-drug conjugates (ADCs), has been introduced to the clinical setting and is currently under intense investigation, alone and in combination with other molecules. This study aims to summarize the latest data on ADCs for lung cancer treatment and to analyze their potential, toxicity profile, and challenges.
Ključne besede: ADC, antibody-drug conjugate, non-small cell lung cancer, small-cell lung cancer, targeted therapy, immunotherapy
Objavljeno v DiRROS: 05.02.2026; Ogledov: 741; Prenosov: 361
.pdf Celotno besedilo (1,73 MB)
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7.
Early-time-point 18F-FDG-PET/CT and other prognostic biomarkers of survival in metastatic melanoma patients receiving immunotherapy
Nežka Hribernik, Katja Strašek, Andrej Studen, Katarina Zevnik, Katja Škalič, Robert Jeraj, Martina Reberšek, 2025, izvirni znanstveni članek

Povzetek: A considerable proportion of metastatic melanoma (mM) patients do not respond to immune checkpoint inhibitors (ICIs). There is a great need to develop noninvasive biomarkers to detect patients, who do not respond to ICIs early during the course of treatment. The aim of this study was to evaluate the role of early [18F]2fluoro- 2-deoxy-D-glucose PET/CT (18F-FDG PET/CT) at week four (W4) and other possible prognostic biomarkers of survival in mM patients receiving ICIs. Patients and methods. In this prospective noninterventional clinical study, mM patients receiving ICIs regularly underwent 18F-FDG PET/CT: at baseline, at W4 after ICI initiation, at week sixteen and every 16 weeks thereafter. The tumor response to ICIs at W4 was assessed via modified European Organisation for Research and Treatment of Cancer (EORTC) criteria. Patients with progressive metabolic disease (PMD) were classified into the no clinical benefit group (no-CB), and those with other response types were classified into the clinical benefit group (CB). The primary end point was survival analysis on the basis of the W4 18F-FDG PET/CT response. The secondary endpoints were survival analysis on the basis of LDH, the number of metastatic localizations, and immune-related adverse events (irAEs). Kaplan-Meier analysis and univariate Cox regression analysis were used to assess the impact on survival. Results. Overall, 71 patients were included. The median follow-up was 37.1 months (95% CI = 30.1–38.0). Three (4%) patients had only baseline scans due to rapid disease progression and death prior to W4 18F-FDG-PET/CT. Fifty-one (72%) patients were classified into the CB group, and 17 (24%) were classified into the no-CB group. There was a statistically significant difference in median overall survival (OS) between the CB group (median OS not reached [NR]; 95% CI = 17.8 months – NR) and the no-CB group (median OS 6.2 months; 95% CI = 4.6 months – NR; p = 0.003). Univariate Cox analysis showed HR of 0.4 (95% CI = 0.18 – 0.72; p = 0.004). median OS was also significantly longer in the group with normal serum LDH levels and the group with irAEs and cutaneous irAEs. Conclusions. Evaluation of mM patients with early 18F-FDG-PET/CT at W4, who were treated with ICIs, could serve as prognostic imaging biomarkers. Other recognized prognostic biomarkers were the serum LDH level and occurrence of cutaneous irAEs.
Ključne besede: melanoma, prognostic biomarkers, survival, immunotherapy
Objavljeno v DiRROS: 21.11.2025; Ogledov: 619; Prenosov: 252
.pdf Celotno besedilo (1,26 MB)

8.
Hymenoptera venom immunotherapy in dogs : safety and clinical efficacy
Ana Rostaher, Nina Maria Fischer, Alessio Vigani, Barbara Šteblaj, Franco Martini, Salina Brem, Claude Favrot, Mitja Košnik, 2023, izvirni znanstveni članek

Povzetek: Insect venom allergy is a potentially life-threatening allergic reaction following a bee, wasp, or ant sting. The only treatment to prevent further systemic sting reactions is venom immunotherapy (VIT), with an efficacy of up to 98% in humans. Prospective clinical data on VIT efficacy in dogs are currently lacking. In this investigation, 10 dogs with severe allergic reactions to either bee or wasp stings were treated with VIT. All dogs tolerated the therapy without adverse effects and the dogs which were re-stung tolerated the sting. This means that VIT is not only safe, but also efficacious in these patients. Furthermore, it was also shown that in addition to skin testing, two serum allergen-specific IgE tests were reliable to identify the underlying patients’ insect sensitization pattern.
Ključne besede: anaphylaxis, angioedema, dogs, Hymenoptera allergy, urticaria, venom immunotherapy
Objavljeno v DiRROS: 03.07.2025; Ogledov: 966; Prenosov: 666
.pdf Celotno besedilo (1,37 MB)
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