Dear colleagues,
I would like to invite you to the lecture by Viktor Valentini "Decoding CuEt-Mediated Immune Activation, Signaling and Immunogenic Changes in Cancer Cells." The lecture will be on Wednesday June 10, 2026 at 9AM in the room 1.09 at IMTM.
Abstract
The involvement of LCK (leukocyte-specific tyrosine kinase) in T-cell receptor signaling is well established, particularly through the phosphorylation of tyrosine residues that regulate its activity. CuEt, a compound with emerging anti-cancer properties, has been shown to activate T-cells and macrophages at nanomolar concentrations. However, the specific intracellular pathways underlying this effect remain to be clarified. Another key issue this kind of activation is that immune cells activated in this manner stop responding to further stimulation if they are treated again at a later time, displaying a state similar to exhaustion. In this study, we investigated the impact of CuEt at nM concentrations on CD8+ T cells aswell as macrophages and the possible immunogenic changes it induces on HCT116 cancer cell line, including both parental and p53-knockout (KO) variants. We are also investigating the specific way of interaction of CuEt with immune cells specifically as we tested CuEt being bound to nanobeads inhibiting its ability to penetrate inside of cells compared to classic in-solution CuEt. Our analysis focused on the phosphorylation status of LCK at tyrosine 394 (activating) and tyrosine 505 (inhibitory) residues. We further examined downstream signaling components such as Zap70, LAT, NFκB and ERK1/2. In addition, we evaluated the expression levels of NKG2D ligands—including ULBP1, ULBP2/5/6, MICA, and MICB—in HCT116 cells to explore potential immunogenic changes induced by CuEt treatment.