Cancer stem cell antigens as targets for new combined anti-cancer therapies

The introduction of immune checkpoint inhibitors (ICI) has ushered in a new, golden age for cancer immunotherapy. However, their clinical success remains limited in several solid cancer types because of the low intrinsic immunogenicity of tumors and the development of immune escape mechanisms. Cancer stem cells (CSC), a small population of cancer cells that are responsible for tumor onset, metastatic spread and relapse after treatment, play a pivotal role in resistance to ICIs. The development of novel therapies that can target CSCs would thus improve the outcomes of current immunotherapy regimens. In this light, vaccines that target CSCs are a promising strategy. This paper briefly describes the immunologic properties of CSCs and their antigenic profile, and reviews current preclinical and clinical approaches that combine CSC-targeting vaccines with different synergistic therapies for the development of more effective antineoplastic treatments.