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16. Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransferUrška Kamenšek, Katja Uršič Valentinuzzi, Boštjan Markelc, Maja Čemažar, Vita Šetrajčič Dragoš, Gregor Serša, 2021, izvirni znanstveni članek Povzetek: In situ vaccination is a promising immunotherapeutic approach, where various local ablative therapies are used to induce an immune response against tumor antigens that are released from the therapy-killed tumor cells. We recently proposed using intratumoral gene electrotransfer for concomitant transfection of a cytotoxic cytokine tumor necrosis factor-% (TNF%) to induce in situ vaccination, and an immunostimulatory cytokine interleukin 12 (IL-12) to boost the primed immune response. Here, our aim was to test the local and systemic effectiveness of the approach in tree syngeneic mouse tumor models and associate it with tumor immune profiles, characterized by tumor mutational burden, immune infiltration and expression of PD-L1 and MHC-I on tumor cells. While none of the tested characteristic proved predictive for local effectiveness, high tumor mutational burden, immune infiltration and MHC-I expression were associated with higher abscopal effectiveness. Hence, we have confirmed that both the abundance and presentation of tumor antigens as well as the absence of immunosuppressive mechanisms are important for effective in situ vaccination. These findings provide important indications for future development of in situ vaccination based treatments, and for the selection of tumor types that will most likely benefit from it.
Ključne besede: in situ vaccination, gene electrotransfer, interleukin 12, tumor necrosis factor [alfa]
Objavljeno v DiRROS: 19.09.2022; Ogledov: 567; Prenosov: 184
 Celotno besedilo (1,78 MB) |
17. Real-world data on detection of germline and somatic pathogenic/likely pathogenic variants in BRCA1/2 and other susceptibility genes in ovarian cancer patients using next generation sequencingVida Stegel, Ana Blatnik, Erik Škof, Vita Šetrajčič Dragoš, Mateja Krajc, Brigita Gregorčič, Petra Škerl, Ksenija Strojnik, Gašper Klančar, Marta Banjac, Janez Žgajnar, Maja Ravnik-Oblak, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.
Ključne besede: BRCA, ovarian cancer, tumor genotyping, HBOC
Objavljeno v DiRROS: 06.09.2022; Ogledov: 545; Prenosov: 287
Celotno besedilo (2,35 MB)
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19. Uporabnost FET PET/CT biomarkerjev pri diagnostiki ponovitve možganskih glialnih tumorjev z različnim statusom IDH mutacijMarija Skoblar Vidmar, Andrej Doma, Uroš Smrdel, Urška Zevnik, Andrej Studen, 2022, objavljeni znanstveni prispevek na konferenci (vabljeno predavanje) Ključne besede: glioblastom, obsevanje, možganski rak, možganski tumor
Objavljeno v DiRROS: 17.06.2022; Ogledov: 568; Prenosov: 187
Celotno besedilo (125,57 KB) |
20. Organoidi glioblastoma kot model za preučevanje odpornosti na terapijoAnamarija Habič, Bernarda Majc, Andrej Porčnik, Roman Bošnjak, Boštjan Markelc, Maja Čemažar, Tamara Lah Turnšek, Barbara Breznik, Metka Novak, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: glioblastom, organoidi, odpornost, možganski rak, možganski tumor, onkologija
Objavljeno v DiRROS: 16.06.2022; Ogledov: 548; Prenosov: 215
Celotno besedilo (80,32 KB) |
