In Science this week, a team led by researchers from Stanford University has shown that the well-known oncogene Myc promotes cancer cell survival by increasing expression of two proteins that prevent a patient's immune system from attacking tumors. Following up on previous research from other groups showing that Myc suppression boosted immune responses against cancer, the investigators discovered that the gene's expression triggered production of PD-L1 and CD47, two immune checkpoint proteins on tumor cell surfaces. They found that when Myc was downregulated, so too were PD-L1 and CD47, while an analysis of gene expression data from a variety of human cancers significantly correlated Myc expression with the proteins' expression in several cancer types. In mouse models, the team also found that Myc inactivation reduced PD-L1 and CD47 expression and improved anti-tumor immune responses.
Also in Science, a Baylor College of Medicine-led group reports on a new model to overcome key obstacles to in vivo mapping of transcription-factor binding to the transcriptional output of a regulated gene. Direct measurement of transcription-factor configuration to promoter activity inside a cell is hindered by probabilistic promoter occupancy, the presence of multiple gene copies, and cell-to-cell variability. To address these issues, the team developed an approach involving the simultaneous measurement, in individual cells, of the concentration of a transcription factor and the number of mRNAs produced from the regulated gene, as well as measurement of how the gene copy number changes throughout the cell cycle. Full single-cell data is then analyzed using a theoretical model that allows for the identification of the contributions of different transcription-factor binding configurations to the stochastic activity of the promoter.