Targeting the Immune Checkpoint in Cancer: Is This a Viable Treatment Option for AML?

The immune suppressive mechanisms displayed by malignant cells are considered a central process in the pathogenesis of cancer. Research in this area has gained significant momentum over the past 20 years, with several immune checkpoints identified, including; CTLA-4, CD200/CD200R, Tim-3/Galectin-9 and PD-L1/PD-1 (Figure 1). Whilst characterising the molecular basis of leukaemia for risk stratification remains at the forefront of AML research; this must now extend to understating how these immune checkpoint pathways fit into the equation. A good example of why this is important is to consider CD200 expression level in AML, which is a negative prognostic indicator [1]. CD200 is an immunosuppressive ligand, that when engaged with its receptor CD200R, has the capacity to attenuate T-cell and NK-cell anti-tumour activity. Interestingly, most cases of CBF AML express high levels of CD200, yet CBF AML performs relatively well clinically. This paradox suggests there is a complex interplay between AML molecular heterogeneity and immune surveillance. Given the recent development and FDA approval of several immune checkpoint therapies, a full understanding of these processes and integration with standard molecular risk stratification is warranted