Bioinformatics Seminar
Time:
Venue: Na
22 September 2020
NaMechanism of Ipatasertib-medicated immunotherapy for triple negative breast cancer at single cell resolution
Jianan WangWEHI Bioinformatics
The phosphoinositide 3-kinase (PI3K)/Akt signalling pathway is a common pathway involved in some important biological processes ; such as cell proliferation ; growth ; and differentiation. Disorders in this pathway can cause tumour cell growth. Ipatasertib is an oral medicine to target and suppress triple negative breast cancer (TNBC) tumours. As an inhibitor of the PI3K/Akt signalling pathway ; Ipatasertib can contribute to suppressing tumour cell proliferation and lead to tumour cell death. Although some clinical trials presented significant results showing that Iparasertib combined with other therapies can prolong patients’ survival time ; the mechanism and immune response of the drug in vivo remains unknown. We performed single-cell RNA sequencing (scRNA-seq) and immune profiling (VDJ sequencing) of 6 ;830 cells from mice treated with ipatasertib and 4 ;210 cells from mice treated with vehicle. Our study aims to investigate the effect of ipatasertib on tumour specific T cell differentiation and on anti-tumour responses. Current results indicate that ipatasertib increases CD8+ T cell frequency and then causes CD8+ T cells to develop into different subtypes of T cells. We also identify enhancement of CD8+ T cell clonal expansion within drug treated samples compared to vehicle treated samples. Further understanding of functional T cell subsets will be essential to improve TNBC immunotherapy.;