Cancer Stem Cells and Anti-tumor Immunity

Abstract

Cancer stem cells (CSCs) are correlated with poor clinical outcomes due to their contribution to chemotherapy resistance and the formation of metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs, which is important for diagnosis, therapy, and prognosis. This review underlines the role of CSCs and circulating tumor cells (CTCs) in tumor relapse and metastasis, the characteristics of CSC and CTC biomarkers, and the techniques used to detect these cells. We also summarized novel therapeutic approaches toward targeting CSCs, especially focusing on the role of immune checkpoint blockades (ICB), such as anti-programmed death 1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PDL1) therapies. Additionally, we address an intriguing new mechanism of action for small molecular drugs, such as telomere-targeted therapy 6-thio-2'deoxyguanosine (6- thio-dG), and how it reshapes tumor microenvironment to overcome ICB resistance. There are indications, that personalized cancer therapy targeting CSC populations in conjunction with immune-mediated strategy hold promise for the removal of residual therapy-resistant CSCs in the near future.

Keywords: Cancer stem cells; anti-tumor immunity; circulating tumor cells; functional assays; immune checkpoint blockades (ICB); surface markers.