Genetic changes are a hallmark of cancer but are particularly prominent in solid tumors compared to liquid tumors. Moreover, tumors that arise in stiffer tissues show more genetic changes than tumors in softer tissues. We developed a method to visualize a common type of genetic change in live cells through application of gene editing, and we use the engineered cells to assess a ‘mechano-genetics’ mechanism for the observed scaling of cancer mutations. Such changes are in principle detectable by the immune system, but checkpoint ligands on cancer cells can passivate attack by immune cells – including a phagocytic synapse. We describe disruption of this macrophage checkpoint that, in a combination treatment strategy, initiates a ‘phagocytic feedback’ loop. In a widely used but challenging pre-clinical model, the approach generates durable cures and anti-tumor immunity.
This seminar will be given online via Zoom. Details in attached poster.