Dendritic Cell-Regulated T Cell Immunity and Tolerance against Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is the most common hematologic malignancy in adults. Although AML patients achieve a complete remission following chemotherapy, most patients relapse with residual disease. Only approximately 25% of AML patients are alive 5 years following their diagnosis. Immunotherapies, such as chimeric antigen receptor T cells, immune checkpoint inhibitors, and vaccination using dendritic cells (DCs) treated by AML cells and their-derived antigens, have emerged as promising therapeutic modalities in AML. However, for AML, in which leukemia cells disseminate in bone marrow (BM), peripheral blood and many other tissues, the mechanisms that regulate the generation and maintenance of leukemia-specific T cell responses are less clear. Growing evidence suggests that AML cells can not only directly repress antigen-specific T cell reactivity, but also induce tolerogenic DCs to reduce tumor-specific T cell responses. DC-mediated tolerogenic mechanisms include suppressing T cell proliferation, inducing T cell deletion and impairing the function of leukemia-specific T cells. Interestingly, this tolerogenic effect can be potentially reversed upon activation by Toll-like receptor agonists and ligation of CD40 in DCs. Clinical studies reveal that DC-based vaccination is potentially effective on preventing and delaying relapse of AML. In this chapter, we focus on discussing these effects of DCs on mediating immunogenicity and immune tolerance of T cells against AML cells.