Immunopathology and Immunotherapy of Myeloid Leukemia Publisher



Snauwaert S¹ ; Rahmani F^{2, 3} ; Vandekerckhove B⁴ ; Kerre T^{5, 6}
Source: Cancer Immunology: Cancer Immunotherapy for Organ-Specific Tumors Published:2020

Abstract

Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells, characterized by maturation arrest, uncontrolled proliferation, and resistance to apoptosis. It is now generally accepted that AML originates from genetic alterations in normal hematopoietic stem cells (HSC) or common myeloid progenitor cells, giving rise to the leukemic stem cell (LSC), from which the bulk of leukemic blasts arise, ultimately leading to the clinical presentation of AML. In the first part of this chapter, the current knowledge on immunopathology of AML is discussed. Genetic alterations in the HSC lead to differentiation block and hyperproliferation, resulting in a number of additive effects that ultimately lead to clinically obvious AML. The current concept of the LSC and the described models for pathogenesis are discussed. The second part covers immunotherapy for AML. An overview of candidate antigens to target in AML is given, followed by the currently described passive and active immunotherapeutic strategies. Active immunotherapy (e.g., modified leukemic cells, peptide, DNA, or dendritic cell-based vaccinations) requires a patient with an intact immune system and can only exploit the available T-cell receptor (TCR) of the patient. Unfortunately, high-affinity TCR-bearing T cells specific to leukemia-associated self-antigens (LAA) are expected to have been deleted after negative selection in the thymus. In addition, the question is whether active immunotherapy will be able to combat the maladaptive changes in the host immune system and tumor microenvironment. Passive immunotherapeutic strategies using adaptive transfer of AML-specific T cells or NK cells are being constantly developed. Adaptive transfer of immune cells to target LAA and minor histocompatibility antigens (MIHA) as well as passive humoral immunity generated through monoclonal antibodies have proven efficacy in AML and sustain hope for the advent of more efficacious treatments. © Springer Nature Switzerland AG 2020. All rights reserved.