The Triple Immune Argument; Surveillance/Evasion/ Senescence and the Increased Incidence of Acute Myeloid Leukemia Observed with Age

Abstract

AML originates from genetic insults of hematopoietic stem and progenitor cells (HSPCs/HSCs) that was identified earlier as leukemia stem cells (LSCs). In quiescent state, trafficking immune cells are crucial for eradication of aberrant clones and obtaining balance between proliferation and apoptosis to maintain HSCs pool. Regulatory T-cells shield the HSCs from the inflammatory reactions by suppressing T-and B-cells. Cancer immunoediting characterize the interaction between the tumor cells and the immune system during cancer evolution. Both branches of the immune system; innate and adaptive can identify AML blasts, eliminating them completely or keeping a balance state that prevents tumor excrescence. However, the AML blasts are struggling to survive and induce many evasion mechanisms ranged from suppression of natural killer and T cytotoxic cells up to the support of suppressor cells and creating a tumor permissive microenvironment. Upon aging, the immune system is restructured in a process termed immunosenescence. The most sticking event in immunosenescence is thymic involution with reduced T-cell output and diversity that will affect the immune surveillance properties, in addition to inflammaging that prepare a convenient environment for the evolution of AML. In this age-impaired immunity background, together with the other age related changes occur in HSPCs and bone marrow microenvironment would initiate and promote the development of AML that is indeed observed in older patients. Realizing this relation would help in proper choice of therapy and the development of new lines of immunotherapy against this difficult disease in that critical age.