A novel combination strategy for effectively targeting cancer stem-like cells.

Abstract

Immunotherapy is now established as the fourth pillar of cancer therapy alongside surgery, radiation and chemotherapy. The major success of cancer immunotherapy to date has been the use of therapies targeting immune checkpoints such as PD-1 and CTLA-4, which act to enhance the ability of tumor-antigen specific CD8+ T cells to target cancer cells.1 Similarly, adoptive cellular therapy of expanded tumor-infiltrating lymphocytes or vaccines based on recognition of tumor (neo)antigens are also promising approaches, which make use of the cytotoxic activity of CD8+ T cells. Although these strategies have shown considerable promise in some patients, the effectiveness of anti-tumor CD8+ T cells is limited by several factors, including local tumor-induced immunosuppression and the requirement of tumors to express MHC-I, which is often downregulated as a tumor escape mechanism.2 Furthermore, the cancer stem cell (CSC) population, reported to be important for tumor progression and metastasis, is known to be resistant to anti-tumor T cells (Figure 1). Therefore, there is a pressing need to develop strategies to further enhance the activity of CD8+ T cells in patients who would otherwise be non-responsive to immunotherapy.