| Naslov: | Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransfer |
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| Avtorji: | ID Kamenšek, Urška (Avtor)
ID Uršič Valentinuzzi, Katja (Avtor)
ID Markelc, Boštjan (Avtor)
ID Čemažar, Maja (Avtor)
ID Šetrajčič Dragoš, Vita (Avtor)
ID Serša, Gregor (Avtor) |
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| Datoteke: |  PDF - Predstavitvena datoteka, prenos (1,78 MB)
MD5: DDCAFACD2C692465513B2DD33C2266FD
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| Jezik: | Angleški jezik |
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| Tipologija: | 1.01 - Izvirni znanstveni članek |
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| Organizacija: |  OI - Onkološki inštitut Ljubljana
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| 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. |
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| Ključne besede: | in situ vaccination, gene electrotransfer, interleukin 12, tumor necrosis factor [alfa] |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Objavljena publikacija |
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| Datum objave: | 28.04.2021 |
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| Založnik: | Elsevier |
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| Leto izida: | 2021 |
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| Št. strani: | str. 1-107831-10-107831 |
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| Številčenje: | Vol. 140 |
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| PID: | 20.500.12556/DiRROS-15561  |
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| UDK: | 602.6/.7 |
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| ISSN pri članku: | 1567-5394 |
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| DOI: | 10.1016/j.bioelechem.2021.107831 |
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| COBISS.SI-ID: | 61967107 |
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| Avtorske pravice: | by Authors |
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| Datum objave v DiRROS: | 19.09.2022 |
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| Število ogledov: | 932 |
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| Število prenosov: | 316 |
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| Metapodatki: |    |
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