Immunologic Approaches to Targeting Cancer Stem Cells

Abstract

Cancer stem cells represent a small subset of tumor cells which have the ability to self-renew and generate the diverse cells that comprise tumors. They are responsible for local tumor recurrence and distant metastasis. The inability to target cancer stem cells with current immune approaches may contribute to treatment failure. Novel immunotherapeutic strategies which specifically target cancer-initiating cells may improve their efficacy. In the implementation of such a strategy, ALDEFLUOR+/ALDHhigh has served as a reliable marker to isolate cancer stem cells from a number of tumor types in animal models and human tumors. Cancer stem cells are resistant to conventional tumor therapy. Nonspecific immunologic targeting of cancer stem cells by NK cells, NKTs, or γδT cells have been reported. In vitro-generated, cancer stem cell-primed T cells specifically targeting cancer stem cells of human xenographs have also been described. Recently, cancer stem cell vaccine has been shown to be capable of inducing protection against tumors in immunocompetent mice. In these models the mechanisms involved specific targeting of cancer stem cells by cancer stem cell-primed T cells and antibodies. Finally, targeting the tumor microenvironment, e.g., IL-6 neutralization or IL-6R blockade, or interrupting the CXCR1/IL-8 interaction may provide novel strategies to enhance immunological targeting of cancer stem cell by T cell and cancer stem cell vaccines. In this chapter, we will review these immunologic approaches to targeting cancer stem cells.