Genetic Engineering Publications - GEG Tech top picks

The immune system can induce metabolic adaptations in tumor cells at an early stage that promote their growth. Researchers identify three proteins that orchestrate this effect: IFNγ, STAT3 and c-Myc. The researchers show that IFNγ activates, in addition to the STAT1-mediated signaling pathway, the STAT3-mediated pathway. This pathway alters the genome expression patterns of the cancer cell by inducing epigenetic changes. It also hyperactivates c-Myc, which is overexpressed in many cancers. The researchers show that genes activated by c-Myc not only shape cancer metabolism, they also compromise T-cell infiltration into tumors and disable their attack on cancer cells. Thus, STAT1- and STAT3-mediated signaling pathways appear to synergize to confer on emerging tumors the ability to avoid immune clearance, resulting in the immunometabolic editing that helps fuel their evolution into full-blown malignancy. The researchers also used CRISPR to screen 2,078 metabolic enzymes in mouse tumors and identified 40 metabolic genes controlled by c-Myc that play an important role in helping cancer cells evade immune surveillance and attack. These enzymes are therefore prime candidates for drug targeting.

A collaborative study led by the Monash Biomedicine Discovery Institute has discovered a new immune checkpoint that could be exploited for cancer treatment. The study shows that by inhibiting the protein tyrosine phosphatase PTP1B in T cells, the body's immune response to cancer can be mobilized, helping to suppress tumor growth. Indeed, this study showed that using a new drug candidate, the abundance of PTP1B in tumor-infiltrating T cells is increased, limiting the ability of T cells to attack tumor cells and fight cancer. These findings identified PTP1B as an intracellular brake, or checkpoint, reminiscent of the PD-1 cell surface checkpoint whose blockade has revolutionized cancer treatment. Furthermore, beyond the improved response to PD-1 blockade, the authors showed that inhibition of PTP1B also significantly improved the efficacy of cell-based therapies using CAR T cells. The authors demonstrate that deletion or inhibition of PTP1B can significantly improve the ability of CAR T cells to attack solid tumors in mice, including breast cancer.