Immunosuppressive Cell Subsets And Factors In Myeloid Leukemias

Simple SummaryEffector immune system cells have the ability to kill tumor cells. However, as a cancer (such as leukemia) develops, it inhibits and evades the effector immune response. Such a state of immunosuppression can be driven by several factors - receptors, soluble cytokines, as well as by suppressive immune cells. In this review, we describe factors and cells that constitute immunosuppressive microenvironment of myeloid leukemias. We characterize factors of direct leukemic origin, such as inhibitory receptors, enzymes and extracellular vesicles. Furthermore, we describe suppressive immune cells, such as myeloid derived suppressor cells and regulatory T cells. Finally, we sum up changes in these drivers of immune evasion in myeloid leukemias during therapy.Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. The following review focuses on main immunosuppressive features of myeloid leukemias. Firstly, factors derived directly from leukemic cells - inhibitory receptors, soluble factors and extracellular vesicles, are described. Further, we outline function, properties and origin of main immunosuppressive cells - regulatory T cells, myeloid derived suppressor cells and macrophages. Finally, we analyze interplay between recovery of effector immunity and therapeutic modalities, such as tyrosine kinase inhibitors and chemotherapy.