Pluto Bioinformatics

GSE117358: RNA-sequencing of pretreatment AB1 (mesothelioma) and Renca (kidney cancer) tumours mice both respondant and non-respondant to immunotherapy with CTLA4 and PD-L1

Bulk RNA sequencing

Purpose: Cancer immunotherapy has shown outstanding results in the past few years. Specifically, antibodies targeting immune checkpoints can prolong survival in some patients with various cancer types. However, most patients do not respond, and it is not fully understood what biological processes determine an effective outcome. This lack of understanding hinders the development of rational combination treatments.; Methods: Here, we analysed bulk RNAseq data obtained from pretreatment responding and non-responding tumour samples from mice treated with antibodies against CTLA4 and PD-L1.; Results: We found that responsive tumours displayed an inflammatory gene expression signaturewhich was consistent with positive upstream regulation by not only IFN/STAT1, but also TLR3 and negative regulation by IL-10. Our results identify a pre-treatment cellular microenvironment and molecular signature associated with benefit from immune checkpoint blockade that can be therapeutically attained to improve treatment efficacy. SOURCE: Emma de Jong (emma.dejong@telethonkids.org.au) - Telethon Kids Institute