The review article "Targeting the Innate Immune System in Pediatric and Adult AML" by Alicia Perzolli, Joost B. Koedijk, C. Michel Zwaan, and Olaf Heidenreich discusses the role of the innate immune system in acute myeloid leukemia (AML) and explores strategies to enhance immunotherapeutic approaches. While T cell-based immunotherapies have shown promise in other cancers, their development for AML has been slow. The review highlights the need to understand the immunosuppressive tumor microenvironment (TME) and the plasticity of innate immune cells such as monocytes, granulocytes, and natural killer (NK) cells. It emphasizes that most studies have focused on T cells, while innate immune cells like macrophages, myeloid-derived suppressor cells (MDSCs), and neutrophils play crucial roles in AML. The article reviews the current knowledge on these innate immune components in AML, their interactions with AML blasts, and how targeting them can improve immunotherapy efficacy. Key findings include the association of M2-like macrophages with therapy resistance, the role of dendritic cells in immune recognition, and the dysregulation of NK cells. The review also discusses strategies to target myeloid cells, manipulate their phenotypes, and block inhibitory receptors to enhance T cell-based immunotherapies. Additionally, it explores the potential of NK cell-based immunotherapies, particularly in pediatric AML, and the challenges and ongoing clinical trials. Overall, the article underscores the importance of understanding and targeting the innate immune system to improve outcomes in AML patients.The review article "Targeting the Innate Immune System in Pediatric and Adult AML" by Alicia Perzolli, Joost B. Koedijk, C. Michel Zwaan, and Olaf Heidenreich discusses the role of the innate immune system in acute myeloid leukemia (AML) and explores strategies to enhance immunotherapeutic approaches. While T cell-based immunotherapies have shown promise in other cancers, their development for AML has been slow. The review highlights the need to understand the immunosuppressive tumor microenvironment (TME) and the plasticity of innate immune cells such as monocytes, granulocytes, and natural killer (NK) cells. It emphasizes that most studies have focused on T cells, while innate immune cells like macrophages, myeloid-derived suppressor cells (MDSCs), and neutrophils play crucial roles in AML. The article reviews the current knowledge on these innate immune components in AML, their interactions with AML blasts, and how targeting them can improve immunotherapy efficacy. Key findings include the association of M2-like macrophages with therapy resistance, the role of dendritic cells in immune recognition, and the dysregulation of NK cells. The review also discusses strategies to target myeloid cells, manipulate their phenotypes, and block inhibitory receptors to enhance T cell-based immunotherapies. Additionally, it explores the potential of NK cell-based immunotherapies, particularly in pediatric AML, and the challenges and ongoing clinical trials. Overall, the article underscores the importance of understanding and targeting the innate immune system to improve outcomes in AML patients.