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Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransferKamenšek, Urška ...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.Source: Bioelectrochemistry. - ISSN 1567-5394 (Vol. 140, 2021, str. 1-107831-10-107831)Type of material - article, component partPublish date - 2021Language - englishCOBISS.SI-ID - 61967107
Author
Kamenšek, Urška |
Uršič Valentinuzzi, Katja, 1990- |
Markelc, Boštjan |
Čemažar, Maja |
Šetrajčič Dragoš, Vita |
Serša, Gregor
Topics
cepljenje in situ |
genski elektrotransfer |
interlevkin 12 |
dejavnik tumorske nekroze [alfa] |
in situ vaccination |
gene electrotransfer |
interleukin 12 |
tumor necrosis factor [alfa]
Author | Kamenšek, Urška ... |
Title | Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransfer |
Publication date | 2021-04-28 |
COBISS.SI-ID | 61967107 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
---|---|---|---|
Spremljanje imunskega odziva v realnem času po in situ vakcinaciji z elektrokemoterapijo in pridruženo gensko terapijo z interlevkinom-12 | J3-8202-2017 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev | P3-0003-2015 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Imunski genski elektroprenos IL-12 in IL-2 za zdravljenje immunološko hladnih/vročih tumorjih | J3-2528-2020 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
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https://dirros.openscience.si/IzpisGradiva.php?id=15561 |
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DRS, in which the journal is indexed
Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Kamenšek, Urška | 28387 |
Uršič Valentinuzzi, Katja, 1990- | 38223 |
Markelc, Boštjan | 32175 |
Čemažar, Maja | 14575 |
Šetrajčič Dragoš, Vita | 51870 |
Serša, Gregor | 08800 |
Source: Personal bibliographies
and: SICRIS
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