Immune surveillance and tumor progression in MM. The immune system plays a crucial role in MM progression through 3 distinct phases. Elimination phase: abnormal PCs are recognized and destroyed by CD8⁺ T cells and NK cells through the release of IFN-γ and perforin. This immune response helps eliminate early malignant PCs, maintaining tumor control. Equilibrium phase: during this phase, immune pressure from CD4⁺ T cells and IL-12 maintains tumor dormancy, keeping myeloma cells in check. However, some myeloma cells survive by gradually reducing their immunogenicity. Escape phase: myeloma cells evade immune destruction by upregulating MHC-I, recruiting immunosuppressive cells (including Tregs, TAMs, and MDSCs), and expressing immune checkpoint molecules (PD-1, CTLA-4, CD160, 2B4). Additionally, soluble inhibitory molecules (MICA, MICB) contribute to immune escape, enabling disease progression. MDSC, myeloid-derived suppressor cell; TAMs, tumor-associated macrophages.