Harnessing the immune system in acute myeloid leukaemia

Abstract

Acute myeloid leukaemia (AML) is an aggressive blood cancer caused by the proliferation of immature myeloid cells. The genetic abnormalities underlying AML affect signal transduction pathways, transcription factors and epigenetic modifiers. In solid tumours, it is emerging that the genetic landscape of the tumour has a direct effect on the anti-tumour immune responses and response to immunotherapeutic treatment. However, there remains little information as to whether genetic abnormalities affect anti-leukemic immune responses. This review discusses current knowledge of AML antigens and immune responses to AML with a particular focus on the role of T cells and natural killer cells. Understanding immune responses to AML has implications for the development and use of immunotherapies to treat AML patients with distinct genetic abnormalities.

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

“…Acute Myeloid Leukemic (AML) cells express several co-stimulatory molecules such as CD80 and CD86 to interact with CTLA4 (cytotoxic T-cell antigen-4)-expressing T cells [27]. In addition, AML cells express immune inhibitory check-points and HLA class I molecules, which contribute to the anti-tumor response exhaustion and immune escape [27, 28].…”

“…Acute Myeloid Leukemic (AML) cells express several co-stimulatory molecules such as CD80 and CD86 to interact with CTLA4 (cytotoxic T-cell antigen-4)-expressing T cells [27]. In addition, AML cells express immune inhibitory check-points and HLA class I molecules, which contribute to the anti-tumor response exhaustion and immune escape [27, 28]. Different approaches have been proposed to harness the anti-tumor response against AML cells, such as antigen-targeted therapies, inhibitory check-points modification and cytokine therapies [27].…”

Antibody darts on target for acute myelogenous leukemia

“…While dramatic remissions might be induced by CD123/DART, the leukemia is notorious for its ability to become resistant to therapy by clonal selection from the highly diverse leukemic population. Resistance could take the form of evolution of clones weakly expressing CD123, or those that successfully edit the immune response (9,10). Whether antibodydirected CD3 cells can avoid leukemic suppression through myeloid-derived suppressor cell-like function, recruitment of regulatory T cells, production of tumor necrosis factor-α or STAT3 based inhibition remains to be seen (25).…”

“…A current question is whether the patient's own immune response can be similarly directed to eliminate leukemia, thus avoiding the need for a transplant. It is clear that AML interacts with the immune system, with the result that an otherwise leukemia-directed T cell attack is suppressed by AML-a process referred to as immune editing (9,10). AML suppresses T cell proliferation through a number of mechanisms: T cells in AML express the checkpoint markers PD1 and Tim3 rendering them susceptible to apoptosis by PD1-L on the leukemia.…”

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients

“…15 T-cell suppression preventing excessive inflammatory response at the site of chronic inflammation depends on an intact PD-1/PD-L1 axis. 16 In the presence of activated T cells, in return, tumor cells upregulate PD-L1, the major mediator of immunosuppression, resulting in inhibition of T helper cell response and "T-cell exhaustion" via the PD-1 pathway.…”