Upregulated Wnt/β-catenin signaling is associated with increased cancer cell resistance and cancer cell-elicited immunosuppression. In non-neoplastic immune cells, upregulated Wnt/β-catenin is, however, associated with either immunosuppression or immunostimulation. Therefore, it is difficult to predict the therapeutic impact inhibitors of Wnt/β-catenin signaling will have when combined with cancer immunotherapy. Here, we evaluated the benefit(s) of the Wnt/β-catenin signaling inhibitor XAV939 in the in vitro elimination of LNCaP prostate cancer cells when cocultured with lymphocytes from patients with localized biochemically recurrent prostate cancer (BRPCa). We found that 5 µM XAV939 inhibited β-catenin translocation to the nucleus in LNCaP cells and CD4+ BRPCa lymphocytes without affecting their proliferation and viability. Preconditioning BRPCa lymphocytes with 5 µM XAV939 accelerated the elimination of LNCaP cells during the coculturing. However, during subsequent re-coculturing with fresh LNCaP cells, BRPCa lymphocytes were no longer able to eliminate LNCaP cells unless coculturing and re-coculturing were performed in the presence of 5 µM XAV939. Comparable results were obtained for PC-3 prostate cancer cells. These findings provide a rationale for combining cell-based immunotherapy of PCa with inhibitors of Wnt/β-catenin signaling.

• MeSH
• beta-katenin antagonisté a inhibitory   metabolismus   MeSH
• buňky PC-3 MeSH
• CD4-pozitivní T-lymfocyty účinky léků   imunologie   MeSH
• heterocyklické sloučeniny tricyklické farmakologie   MeSH
• imunoterapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty farmakoterapie   genetika   patologie   MeSH
• proteiny Wnt antagonisté a inhibitory   metabolismus   MeSH
• protinádorové látky farmakologie   MeSH
• senioři MeSH
• signální dráha Wnt účinky léků   MeSH
• T-lymfocyty cytologie   imunologie   MeSH
• tankyrasy antagonisté a inhibitory   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-katenin MeSH
• CTNNB1 protein, human MeSH Prohlížeč
• heterocyklické sloučeniny tricyklické MeSH
• proteiny Wnt MeSH
• protinádorové látky MeSH
• tankyrasy MeSH
• XAV939 MeSH Prohlížeč