Urška Kamenšek (Avtor), Katja Uršič (Avtor), Boštjan Markelc (Avtor), Maja Čemažar (Avtor), Vita Šetrajčič Dragoš (Avtor), Gregor Serša (Avtor)

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

cepljenje in situ;genski elektrotransfer;interlevkin 12;dejavnik tumorske nekroze [alfa];in situ vaccination;gene electrotransfer;interleukin 12;tumor necrosis factor [alfa];

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: OI - Onkološki inštitut Ljubljana
Založnik: Elsevier
UDK: 602.6/.7
COBISS: 61967107 Povezava se bo odprla v novem oknu
ISSN: 1567-5394
Št. ogledov: 62
Št. prenosov: 19
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: cepljenje in situ;genski elektrotransfer;interlevkin 12;dejavnik tumorske nekroze [alfa];
Strani: str. 1-107831-10-107831
Zvezek: ǂVol. ǂ140
Čas izdaje: 2021
DOI: 10.1016/j.bioelechem.2021.107831
ID: 16506324