Effect of pharmacological BCL-2 inhibition with venetoclax on T cell homeostasis [RNA-seq]

Venetoclax, a BCL-2 inhibitor, is being increasingly used in the clinic as a single agent or in combination. Thus far, there has been little to show how this drug affects the immune system. Research has been done to characterize the mechanisms of resistance of cancer cells to venetoclax, however, an immune subset of T cells called regulatory T cells has also shown resistence to apoptotic cell death via venetoclax administration. To investigate the effects of venetoclax on the transcriptional landscape of regulatory T cells (with some comparison to conventional T cells), we treated FOXP3-IRES-GFP mice for 14 days with 50mg/kg of venetoclax and analyzed their RNA profiles. We observed that Treg cells upregulate genes involved in Th17 effector cell differentiation, which was not observed in the Tcon counterparts. RNA-seq of CD4+ FOXP3- Tcons and CD4+ FOXP3+ Tregs following treatment with venetoclax