Immunity to stemness genes in human cancer

Abstract

A growing body of data points to not only intraclonal heterogeneity and hierarchy of growth potential, but also plasticity of cellular differentiation within human tumors. Recent studies have also identified surprising overlap between pathways that regulate pluripotency in embryonal stem (ES) cells and oncogenesis. While there is a long history of targeting embryonal tissues toward cancer vaccines, recent identification of crucial stemness pathways in ES cells as well as putative cancer stem cells (CSCs) provides novel opportunities for antigen-specific targeted therapy. Here we discuss recent insights into the capacity of the immune system to target these pathways. Immunologic targeting of pathways associated with stemness has implications for both immune regulation of tumor growth as well as regenerative therapies with embryonal stem cells.

Figure 1

Relationship between pluripotency and tumorigenicity in regenerative medicine. The capacity of stem cells to induce tumors in the host is directly proportional to their pluripotency.

Figure 2

Embryonal stem cell antigens as targets of cancer immunity. Genes restricted to ES cells and cancer, but not expressed by normal adult stem cells or their differentiated progeny (shaded area) may be potential targets for cancer vaccines. Some of these genes can regulate stemness in both cancer and ES cells, and are the most attractive targets.