Dormancy and cancer immunoediting in PC dyscrasias. (A) The BM osteoblastic niche induces dormancy in malignant PCs. Note that other immune cells in the PC niche might also contribute to cellular dormancy. Enhanced osteoclast activity and inflammation signaling can abrogate the niche-induced dormancy. (B) Lack of sufficient blood supply renders functional dormancy, called angiogenic dormancy. In addition to the bidirectional interaction between MM cells and MSCs, tumor-associated macrophages (TAMs) contribute to the generation of proangiogenic factors. In response to these stimuli, endothelial progenitor cells and TAMs cooperatively generate neovasculature, which might trigger the growth of MM. (C) Cytotoxic lymphocytes, such as natural killer cells and CD8⁺ T cells, critically contribute to the immunosurveillance of malignantly transformed cells in the elimination phase. In the equilibrium phase, immune-mediated functional dormancy prevents outgrowth of malignant PCs, which might represent MGUS and SMM. In active MM, malignant PCs eventually overwhelm the immune system, leading to development of the immunosuppressive milieu (the escape phase). Reentry into the equilibrium phase can be achieved by remission-induction therapy, which can contribute to long-term minimal residual disease (MRD) control in some patients. However, the immunosuppressive milieu is reestablished after relapse.