Figure 2.

Possible mechanisms of post-transplant immune evasion. Loss of AML immunogenicity under immune selective pressure following allo-SCT leads to immune escape and relapse. There are multiple possible mechanisms: (A) Reduction in HLA presentation prevents donor-derived T cells identifying the AML cell. This is commonest in HLA-mismatched transplants and can result from genetic loss of part, or all, of the HLA locus. In other patients, downregulation of HLA expression via defects in transcriptional regulators may play a role. (B) Upregulation of immune checkpoint inhibitory molecules has been shown to suppress T cell responses at relapse in a subset of patients. Expression of anti-inflammatory enzymes (C) and cytokines, and suppression of pro-inflammatory cytokines (D), have an immunosuppressive effect in AML but their role is yet to be established in the allo-SCT setting. Created with BioRender.com.