Thus, only CSCs may be able to seed tumors in patients with functional immunosurveillance, and immune privilege may be a key criterion for identifying CSCs.[18] Furthermore, the model suggests that CSCs may initially be dependent on stem cell niches, and CSCs may function there as a reservoir in which mutations can accumulate over decades unrestricted by the immune system. Clinically overt tumors may grow if: A) CSCs lose their dependence on niche factors (less differentiated tumors), B) their offspring of highly proliferative, yet initially immunogenic normal tumor cells evolve means to escape immunosurveillance or C) the immune system may lose its tumorsuppressive capacity, e.g. due to ageing.[18]