The Immune Resistance Signature of Acute Myeloid Leukemia and Current Immunotherapy Strategies

Simple Summary Acute myeloid leukemia (AML) is an aggressive cancer of stem cells originating in the bone marrow. Increasing evidence suggests that AML survival and relapse are controlled by genetic alterations, as well as a functional interaction between the tumor and the immune system. In this review, we will discuss the biology of immune evasion in AML and explore the current landscape of immune-based therapies. We argue that a better understanding of the immune microenvironment in AML could help predict responses to immunotherapy and guide decisions for future treatment.Abstract Acute myeloid leukemia (AML) is a complex hematopoietic clonal disorder with limited curative options beyond stem cell transplantation. The success of transplant is intimately linked with the graft versus leukemia effect from the alloreactive donor immune cells including, T and NK cells. The immune system plays a dynamic role in leukemia survival and resistance. Despite our growing understanding of the immune microenvironment, responses to immune-based therapies differ greatly between patients. Herein, we review the biology of immune evasion mechanisms in AML, discuss the current landscape of immunotherapeutic strategies, and discuss the implications of therapeutic targets. This review focuses on T and NK cell-based therapy, including modified and non-modified NK cells, CAR-T and CAR-NK cells, antibodies, and checkpoint blockades. Understanding the complex interchange between immune tolerance and the emergence of tumor resistance will improve patient outcomes.