The PKM2 activator and molecular glue TP-1454 modulates tumor-immune responses by destabilizing T-regulatory cells

Background: Pyruvate kinase is an important enzyme that catalyzes the last step of glycolysis. The M2 isoform (PKM2) is important for balancing respiration and biosynthesis, which can be achieved by switching between the highly active tetrameric form and the less active dimeric form through allosteric metabolite binding. In addition to its role in metabolic regulation, the dimeric form of PKM2 can translocate to the nucleus, altering transcription to enhance cancer cells' ability to grow and evade immune detection.