Expression profiling by high throughput 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 signature which was consistent with positive upstream regulation by not only IFNγ/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.
48 samples in total: 24 samples from AB1 pretreatment tumours (12 responders, 12 non-responders) and 24 samples from Renca pretreatment tumours (12 responders, 12 nonresponders). Each sample represents an individual biological replicate (i.e. no duplicate samples from the same mouse). Response to immunotherapy determined….