Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma.

George A Ward Zhiqiang Zhang Simone Jueliger Ilya S Potapov Matthew P Davis Adam R Boxall Jason Taylor Harold N Keer Andrea Biondo John F Lyons Martin Sims Tomoko Smyth

Published in: Cancer research communications (2024)

The IAP antagonist tolinapant can induce necroptosis, a key immune-activating event, in TCL. Combination with DNA hypomethylation enhances tolinapant sensitivity and primes resistant cells by re-expressing necrosome proteins. In addition, this combination leads to increases in genes involved in IFN signaling and neoantigen expression, providing further molecular rationale for this novel therapeutic option.

Keyphrases

induced apoptosis
poor prognosis
single molecule
signaling pathway
cell cycle arrest
dna methylation
gene expression
circulating tumor
immune response
clinical trial
binding protein
oxidative stress
long non coding rna
pi k akt
circulating tumor cells