Molecular mechanisms of PD-1 immune checkpoint inhibitors in mouse mammary tumours

Understanding the molecular actions of anti-PD-1 immune checkpoint inhibitors in ER+ mouse mammary tumours is crucial to aid in understanding of how this treatment can be used in ER+ breast cancer. Here, we demonstrate that treatment of mouse mammary tumours with anti-PD-1 alone results in limited genome wide transcriptional changes. Treatment with the endocrine therapy, letrozole, results in large genome wide transcriptional changes with predominant influence on oestrogen responsive genes and genes involved in cell cycle related processes. Further, we report that treatment with a combination of both letrozole and anti-PD-1 results again produced large genome wide transcriptional changes, all of which were observed upon letrozole treatment alone. To investigate the transcriptional effects of anti-PD-1 and letrozole treatments, we transcriptionally profiled SSM3 ER+ breast cancer tumours in immunocompetent 129/SvEv mice treated with either letrozole alone, anti-PD-1 alone, letrozole + anti-PD-1 or a vehicle control. RNA-seq was conducted on RNA was extracted from five biological replicates of each treatment.