Mechanisms of immune escape of leukemia
| Invasion of immunologically privileged sites: CNS, gonads |
| Down-regulation of HLA class I and class II expressions |
| Deficient processing and presentation of peptides |
| Deficient expression of costimulatory molecules: CD80, CD83, CD86, CD40, LFA-1, ICAM |
| Secretion of inhibitory cytokines by leukemia cells: IL-10, TGF-β |
| Abnormal secretion of and resistance to pro-inflammatory cytokines: TNF-α, IFN-γ |
| Nonfunctional FAS on leukemia cells |
| FAS-L expression by leukemia cells |
| Regulatory T cells and production of indoleamin 2,3-dioxygenase (IDO) by leukemia cells |
| Down-regulation of ζ-chain (lymphoma and CML) and ϵ-chain (CML) of the T-cell receptor |
| Down-regulation of CD28 in AML |
| Down-regulation of IL-2 receptor |
| Low IL-2 |
| Apoptosis of high-avidity T cells |
| Invasion of immunologically privileged sites: CNS, gonads |
| Down-regulation of HLA class I and class II expressions |
| Deficient processing and presentation of peptides |
| Deficient expression of costimulatory molecules: CD80, CD83, CD86, CD40, LFA-1, ICAM |
| Secretion of inhibitory cytokines by leukemia cells: IL-10, TGF-β |
| Abnormal secretion of and resistance to pro-inflammatory cytokines: TNF-α, IFN-γ |
| Nonfunctional FAS on leukemia cells |
| FAS-L expression by leukemia cells |
| Regulatory T cells and production of indoleamin 2,3-dioxygenase (IDO) by leukemia cells |
| Down-regulation of ζ-chain (lymphoma and CML) and ϵ-chain (CML) of the T-cell receptor |
| Down-regulation of CD28 in AML |
| Down-regulation of IL-2 receptor |
| Low IL-2 |
| Apoptosis of high-avidity T cells |
Different mechanisms can contribute to the failure of DLT to eradicate leukemia. Leukemia cells may persist in immunologically privileged sites, such as the CNS and gonads, or in extramedullary sites, such as the skin or the kidney, while still showing a continued remission in marrow. Malignant cells may escape immune detection and elimination if they have an altered expression of target antigens or costimulatory molecules required for efficient recognition. They may also directly down-regulate effector cells through secretion of inhibitory cytokines. Modulation of expression of FAS or FAS-ligand can also contribute to tumor escape from immune control.