Targeting CSCs has been in the focus of research for many years (13). As reviewed by Shibata and Hoque, the combination of CSC-targeted therapies and conventional non-targeted therapies can result in a decreased chemoresistance (9). Approaches of CSC-targeted therapies include kinase inhibitors as well as targeting stem cell associated pathways such as Wnt and β-catenin, some of which have already entered the clinical phase (9, 13). Immunological approaches that target CSCs via MHC-restricted killing include adoptive cell transfer, targeting checkpoint inhibitors as well as antibody-based approaches and vaccination. MHC-unrestricted killing based on NK-, γδT-, and chimeric antigen receptor (CAR) T-cell approaches have been established (561, 562). Currently, these approaches are performed after failures of the first-line therapies.