Immune System Influence on Hematopoietic Stem Cells and Leukemia Development

Hematopoietic stem cells (HSCs) are the source for all blood cells, including immune cells, and they interact dynamically with the immune system. This chapter will explore the nature of stem cells, particularly HSCs, in the context of their immune microenvironment. The dynamic interactions between stem cells and the immune system can have profound implications for current and future therapies, particularly regarding a potential "immune-privileged" HSC microenvironment. Immune/stem cell interactions change during times of stress and injury. Recent advances in cancer immunotherapy have overturned the long-standing belief that, being derived from the self, cancer cells should be immunotolerant. Instead, an immunosurveillance system recognizes and eliminates emergent pre-cancerous cells. Only in the context of a failing immunosurveillance system does cancer fully develop. Combined with the knowledge that stem cells or their unique properties can be critically important for cancer initiation, persistence, and resistance to therapy, understanding the unique immune properties of stem cells will be critical for the development of future cancer therapies. Accordingly, the therapeutic implications for leukemic stem cells (LSCs) inheriting an immune-privileged state from HSCs will be discussed. Through their dynamic interactions with a diverse immune system, stem cells serve as the light and dark root of cancer prevention vs. development.