Targeting the innate immune system in pediatric and adult AML

Abstract

While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, the development of immunotherapies for both adult and pediatric AML has been relatively slow and limited. In addition to the need to identify suitable target antigens, a better understanding of the immunosuppressive tumor microenvironment is necessary for the design of novel immunotherapy approaches. To date, most immune characterization studies in AML have focused on T cells, while innate immune lineages such as monocytes, granulocytes and natural killer (NK) cells, received less attention. In solid cancers, studies have shown that innate immune cells, such as macrophages, myeloid-derived suppressor cells and neutrophils are highly plastic and may differentiate into immunosuppressive cells depending on signals received in their microenvironment, while NK cells appear to be functionally impaired. Hence, an in-depth characterization of the innate immune compartment in the TME is urgently needed to guide the development of immunotherapeutic interventions for AML. In this review, we summarize the current knowledge on the innate immune compartment in AML, and we discuss how targeting its components may enhance T cell-based- and other immunotherapeutic approaches.

Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges

“…Similar to solid tumors, pediatric AML blasts increase the number of MDSCs, drive macrophages toward a pro-tumoral phenotype, and exhibit signs of exhausted NK cells [ 14 , 19 ]. The correlation of NK cell infiltration and activation with enhanced outcomes in pediatric leukemia is well-documented in studies, thus sparking considerable interest in NK cell-based immunotherapies for this ailment [ 20 ].…”