Roles of immune cells in LTS MM
| Immune cell type . | Role in immune surveillance . | Changes in LTS MM . | Therapeutic modulation . |
|---|---|---|---|
| T cells (CD8+) | Direct cytotoxicity against myeloma cells via perforin/granzyme release, cytokine production (IFN-γ, TNF-α) | Increased CD8+ T-cell counts, reduced Tregs, enhanced effector memory subsets, improved polyfunctional response | Pomalidomide enhances CD8+ T-cell activation, reduces Tregs, and promotes T-cell persistence. Checkpoint inhibitors (anti–PD-1/PD-L1) may further improve exhausted T cells |
| T cells (CD4+) | Helper function, cytokine release (IL-2, IL-21), support for CD8+ T cells and B-cell activation | Shift toward Th1/Th17 responses, reduced Tfh (follicular helper) support for myeloma-promoting B cells, functional Treg suppression | IL-2 agonists promote effector T-cell expansion while reducing suppressive Tregs. IMiDs (eg, lenalidomide, pomalidomide) modulate CD4+ T-cell function |
| NK cells | Cytotoxicity against myeloma cells via natural killing mechanisms, secretion of proinflammatory cytokines (IFN-γ, TNF-α) | Altered phenotype with increased CCL3/CCL4/CCL5 secretion, signs of exhaustion (elevated TIGIT, NKG2A) | IL-15 and mAbs targeting NK exhaustion markers (eg, anti-NKG2A) enhance NK function |
| B cells | Antigen presentation, production of myeloma-specific antibodies, regulatory functions | Partial recovery of naïve and memory B-cell subsets, reduced Bregs, which lowers immunosuppressive effects | Pomalidomide increases B1b cells, modulates Breg function, and enhances antigen presentation, contributing to an improved antimyeloma response |
| Immune cell type . | Role in immune surveillance . | Changes in LTS MM . | Therapeutic modulation . |
|---|---|---|---|
| T cells (CD8+) | Direct cytotoxicity against myeloma cells via perforin/granzyme release, cytokine production (IFN-γ, TNF-α) | Increased CD8+ T-cell counts, reduced Tregs, enhanced effector memory subsets, improved polyfunctional response | Pomalidomide enhances CD8+ T-cell activation, reduces Tregs, and promotes T-cell persistence. Checkpoint inhibitors (anti–PD-1/PD-L1) may further improve exhausted T cells |
| T cells (CD4+) | Helper function, cytokine release (IL-2, IL-21), support for CD8+ T cells and B-cell activation | Shift toward Th1/Th17 responses, reduced Tfh (follicular helper) support for myeloma-promoting B cells, functional Treg suppression | IL-2 agonists promote effector T-cell expansion while reducing suppressive Tregs. IMiDs (eg, lenalidomide, pomalidomide) modulate CD4+ T-cell function |
| NK cells | Cytotoxicity against myeloma cells via natural killing mechanisms, secretion of proinflammatory cytokines (IFN-γ, TNF-α) | Altered phenotype with increased CCL3/CCL4/CCL5 secretion, signs of exhaustion (elevated TIGIT, NKG2A) | IL-15 and mAbs targeting NK exhaustion markers (eg, anti-NKG2A) enhance NK function |
| B cells | Antigen presentation, production of myeloma-specific antibodies, regulatory functions | Partial recovery of naïve and memory B-cell subsets, reduced Bregs, which lowers immunosuppressive effects | Pomalidomide increases B1b cells, modulates Breg function, and enhances antigen presentation, contributing to an improved antimyeloma response |
Bregs, regulatory B cells; PD-L1, programmed cell death ligand 1; TNF-α, tumor necrosis factor-α.