The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes

Figure 1

Immune mechanisms in MDS. Early (low risk) MDS. (1) Malignant MDS cells (M) induce clonal expansion of CD8+ T-cells (T). (2) CD-8+ T-cells produce cytokines like TNF-a and INF-Y. (3) This results in apoptosis in hematopoietic stem cells (HSC) resulting in cytopenias but also keep MDS cells (M) from proliferating. (4) MSC in normal hematopoiesis suppress T-cell activation, a process that is aberrant in MDS. (5) MSC also produce proinflammatory cytokines. Late (high risk) MDS. (6) While continued inflammation leads to more apoptosis of hematopoietic stem cells (HSC) and cytopenias worsen, TNF-a and INF-Y start inducing PDL-1 expression on MDS clonal cells. (7) PD-L1 allows the MDS cells to escape immune surveillance by T-cell suppression. AML. (8) MDS transitions into acute myeloid leukemia (AML).