20.500.12556/DiRROS-15561 Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransfer 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. in situ vaccination gene electrotransfer interleukin 12 tumor necrosis factor [alfa] cepljenje in situ genski elektrotransfer interlevkin 12 dejavnik tumorske nekroze [alfa] true false true Elsevier Angleški jezik Slovenski jezik by Authors Neznano 2022-09-17 03:40:15 2022-09-19 10:20:11 2022-09-30 15:13:13 0000-00-00 00:00:00 2021 0 0 str. 1-107831-10-107831 Vol. 140 2021 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2021-04-28 602.6/.7 1567-5394 10.1016/j.bioelechem.2021.107831 61967107 RAZ_Kamensek_Urska_2021.pdf RAZ_Kamensek_Urska_2021.pdf 1 DDCAFACD2C692465513B2DD33C2266FD ec5fe955687defda49e53c35a71f3003f36f0196e97a1b0a4ad1b6c626f5cea4 439ee31d-37e3-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20583 Onkološki inštitut Ljubljana 0 0 0