Acute myeloid leukemia (AML) is a rapidly progressive, poor-prognosis malignancy arising from hematopoietic stem/progenitor cells. The long history of successful use of allogeneic hematopoietic cell transplantation (alloHCT) in AML indicates that this disease is immunoresponsive, leading to optimism that novel immunotherapies such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors will generate meaningful disease control. However, emerging data on the immunoevasive tactics employed by AML blasts at diagnosis and at relapse indicate that optimism must be tempered by an understanding of this essential paradox. Furthermore, AML has a low mutational burden, thus presenting few neoantigens for attack by autologous T cells even after attempted reversal of inhibitory receptor/ligand interactions. In this review we outline the known AML targets, explore immune evasion mechanisms, and describe recent data and current clinical trials of single and combination immunotherapies.
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