Targeting the Immune Microenvironment in Acute Myeloid Leukemia: A Focus on T Cell Immunity

Adam J. Lamble, Evan F. Lind

Immunotherapies, such as chimeric antigen receptor T cells, bispecific antibodies, and immune checkpoint inhibitors, have emerged as promising modalities in multiple hematologic malignancies. Despite the excitement surrounding immunotherapy, it is currently not possible to predict which patients will respond. Within solid tumors, the status of the immune microenvironment provides valuable insight regarding potential responses to immune therapies. Much less is known about the immune microenvironment within hematologic malignancies but the characteristics of this environment are likely to serve a similar predictive role. Acute myeloid leukemia (AML) is the most common hematologic malignancy in adults, and only 25% of patients are alive 5 years following their diagnosis. There is evidence that manipulation of the immune microenvironment by leukemia cells may play a role in promoting therapy resistance and disease relapse. In addition, it has long been documented that through modulation of the immune system following allogeneic bone marrow transplant, AML can be cured, even in patients with the highest risk disease. These concepts, along with the poor prognosis associated with this disease, have encouraged many groups to start exploring the utility of novel immune therapies in AML. While the implementation of these therapies into clinical trials for AML has been supported by preclinical rationale, many questions still exist surrounding their efficacy, tolerability, and the overall optimal approach. In this review, we discuss what is known about the immune microenvironment within AML with a specific focus on T cells and checkpoints, along with their implications for immune therapies.