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Naslov:Electrochemotherapy with bleomycin, oxaliplatin, or cisplatin in mouse tumor models, from tumor ablation to in situ vaccination
Avtorji:ID Uršič Valentinuzzi, Katja (Avtor)
ID Kamenšek, Urška (Avtor)
ID Kranjc Brezar, Simona (Avtor)
ID Heranney, Chloe (Avtor)
ID Komel, Tilen (Avtor)
ID Buček, Simon (Avtor)
ID Čemažar, Maja (Avtor)
ID Serša, Gregor (Avtor)
Datoteke:.pdf PDF - Predstavitvena datoteka, prenos (18,91 MB)
MD5: 7EF67125763B3465C247C28B50A9DCF8
 
URL URL - Izvorni URL, za dostop obiščite https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1470432/full
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo OI - Onkološki inštitut Ljubljana
Povzetek:Introduction: In addition to its direct cytotoxic effects, ablative therapies as electrochemotherapy (ECT) can elicit indirect antitumor effects by triggering immune system responses. Here, we comprehensively analyzed this dual effectiveness of intratumoral ECT with chemotherapeutic drugs bleomycin (BLM), oxaliplatin (OXA), and cisplatin (CDDP). Our aim was to determine if ECT can act as in situ vaccination and thereby induce an abscopal effect. By evaluating ECT’s potential for in situ vaccination, our goal was to pave the way for future advancements for its combination with emerging (immuno)therapies, leading to enhanced responses and outcomes. Methods: We employed two mouse tumor models, the immunologically cold B16F10 melanoma and 4T1 mammary carcinoma, to explore both local and systemic (i.e., abscopal) antitumor effects following equieffective intratumoral ECT with BLM, OXA, and CDDP. Through histological analyses and the use of immunodeficient and metastatic (for abscopal effect) mouse models, we identified and compared both the cytotoxic and immunological components of ECT’s antitumor efficiency, such as immunologically recognizable cell deaths (immunogenic cell death and necrosis) and immune infiltrate (CD11+, CD4+, CD8+, GrB+). Results: Differences in immunological involvement after equieffective intratumoral ECT were highlighted by variable kinetics of immunologically recognizable cell deaths and immune infiltrate across the studied tumor models. Particularly, the 4T1 tumor model exhibited a more pronounced involvement of the immune component compared to the B16F10 tumor model. Variances in the antitumor (immune) response were also detected based on the chemotherapeutic drug used in ECT. Collectively, ECT demonstrated effectiveness in inducing in situ vaccination in both tumor models; however, an abscopal effect was observed in the 4T1 tumor model only. Conclusions: This is the first preclinical study systematically comparing the immune involvement in intratumoral ECT’s efficiency using three distinct chemotherapeutic drugs in mouse tumor models. The demonstrated variability in immune response to ECT across different tumor models and chemotherapeutic drugs provides a basis for future investigations aimed at enhancing the effectiveness of combined treatments.
Ključne besede:electroporation, chemotherapeutic drugs, mouse tumor models
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Poslano v recenzijo:25.07.2024
Datum sprejetja članka:24.01.2025
Datum objave:11.02.2025
Kraj izida:Lausanne
Založnik:Frontiers Media SA
Leto izida:2025
Št. strani:str. [1-17]
Številčenje:Vol. 16
Izvor:Lausanne, Switzerland
PID:20.500.12556/DiRROS-23752 Novo okno
UDK:602
ISSN pri članku:1664-3224
DOI:10.3389/fimmu.2025.1470432 Novo okno
COBISS.SI-ID:226331395 Novo okno
Avtorske pravice:by Authors
Opomba:Nasl. z nasl. zaslona; Opis vira z dne 10. 2. 2025;
Datum objave v DiRROS:19.11.2025
Število ogledov:165
Število prenosov:77
Metapodatki:XML DC-XML DC-RDF
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Gradivo je financirano iz projekta

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P3-0003-2022
Naslov:Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:Z3-2651-2020
Naslov:Elektrokemoterapija kot in situ vakcinacija

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:elektroporacija, kemoterapevtiki, mišji tumorski modeli


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