This study examined the relationship between cancer stem cell (CSC) markers and melanoma response to immunotherapy. Immunotherapy has emerged as a key anti-cancer therapy. It has demonstrated marked survival benefits in patients with advanced melanoma. However, there remains a significant number of patients who do not respond to treatment. Therefore, it is a priority to unravel the mechanisms underlying the emergence of drug resistance. One key players that may have a significant role in the development of drug resistance are the CSCs.
Transcriptomic profiles of 158 melanoma biopsies from patients treated with anti-programmed cell death 1 ligand-1 (PD-1) monotherapy (nivolumab or pembrolizumab; n = 63) or combined anti-PD-1 and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4; ipilimumab; n = 57) were obtained. Patients were categorised as responders or non-responders using the Response Evaluation Criteria in Solid Tumors (RECIST), where responders had a complete response (CR), partial response (PR), or stable disease (SD) of greater than 6 months with no disease progression. Samples were analysed for differential gene expression after normalisation using DESeq2 and HTSeq. Gene levels of well-defined CSCs were compared between responders and non-responders. Changes to gene expression levels were also compared pre and post immunotherapy treatment.
This analysis identified a unique melanoma CSC marker gene expression “signature” that corresponds to a positive response to immune checkpoint inhibitors. This signature was associated with a significantly longer progression-free survival. Therefore, we have identified a CSC gene signature that can be used to predict patient response to the current available anti-PD-1 or anti-CTLA4 based therapies. Furthermore, this helps with identifying patients in need of other therapeutic strategies.