Altogether, these data support the investigation of a miR-186-containing nanoparticle formulation to prevent tumor growth and TGFβ1-dependent immune escape in high-risk neuroblastoma patients as well as the inclusion of <i>ex vivo</i>-derived NK exosomes as a potential therapeutic option alongside NK cell-based immunotherapy.<b>Significance:</b> These findings highlight the therapeutic potential of NK cell-derived exosomes containing the tumor suppressor miR-186 that inhibits growth, spreading, and TGFβ-dependent immune escape mechanisms in neuroblastoma.
The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined.
In this study we used a NB cell line (LAN-5) which has been shown to partially respond to TGFbeta and to present high levels of TGFbeta receptor type I and low levels of receptor type II (TbetaRII) on the cell surface.
To analyse the TGF-beta response in neuroblastoma, the expression of TGF-beta1 and TGF-beta type I, II and III receptor genes was investigated in 61 cancer samples by means of reverse transcription polymerase chain reaction.
These results suggest the hypothesis that: (a) induction of a TGF-beta 1 negative autocrine growth loop may be a necessary component for RA-responsiveness of neuroblastoma cells in vivo; and (b) the inability to induce or maintain this TGF-beta 1 negative autocrine growth loop may be a mechanism of RA resistance in neuroblastoma.
Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection.