Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells

SIMPLE SUMMARY: Cancer stem cells (CSCs) are regarded as the root of tumor development and drug resistance. Accumulating evidence shows that the behaviors of CSCs are highly regulated by stromal cells within the tumor microenvironment (TME), and concurrently CSCs regulate the function of various immune cells. In this review, we focus on the crosstalk between stroma cells and cancer cells, which leads to CSC expansion, drug resistance and immune evasion. Understanding the role of stromal cells in regulation of the above processes reveals novel potential therapeutic strategy against cancer. ABSTRACT: Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.