title: Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.
abstract: Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body's own immune system to fight leukemic cells.
authors.forename: Hanna A
authors.initials: HA
authors.lastname: Knaus
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kanakry
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.affiliation: Cancer Research Building I, Room 346, 1650 Orleans Street, Baltimore, MD 21287, United States.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gojo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002986:Clinical Trials as Topic; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte
keywords: Acute lymphoblastic leukemia; T cells.; acute myeloid leukemia; co-inhibitory receptor; immune
  evasion; immune checkpoint pathway; immunotherapy; monoclonal antibody