Checkpoint Inhibitors in Acute Myeloid Leukemia

Abstract

The prognosis of acute myeloid leukemia (AML) remains unsatisfactory. Among the reasons for the poor response to therapy and high incidence of relapse, there is tumor cell immune escape, as AML blasts can negatively influence various components of the immune system, mostly weakening T-cells. Since leukemic cells can dysregulate immune checkpoints (ICs), receptor-based signal transductors that lead to the negative regulation of T-cells and, eventually, to immune surveillance escape, the inhibition of ICs is a promising therapeutic strategy and has led to the development of so-called immune checkpoint inhibitors (ICIs). ICIs, in combination with conventional chemotherapy, hypomethylating agents or targeted therapies, are being increasingly tested in cases of AML, but the results reported are often conflicting. Here, we review the main issues concerning the immune system in AML, the main pathways leading to immune escape and the results obtained from clinical trials of ICIs, alone or in combination, in newly diagnosed or relapsed/refractory AML.

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies

“…Finally, FAB-M4/M5 AML cells show a high expression of several chemokines involved in local T-cell chemotaxis [ 49 , 50 ]. Although effector T cells can mediate antileukemic effects (even though escape mechanisms may also exist) [ 66 , 67 , 68 ], activated T cells can also release cytokines that mediate direct (i.e., antiapoptotic hematopoietic growth factors), as well as indirect (e.g., recruitment/differentiation of M2-like macrophages), AML-supporting effects [ 69 ]. However, to the best of our knowledge, no previous studies have investigated whether the extracellular stroma or the composition/education of nonleukemic bone marrow cells differ between FAB-M4/M5 patients and other AML patients.…”

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

“…Several drugs targeting this pathway, blocking PD1 (Nivolumab, Pembrolizumab, and Cemiplimab) or PDL1 (Atezolizumab, Avelumab, and Durvalumab), have been successfully tested and approved by the FDA in solid cancers and hematologic malignancies [89,111], although none of these have been approved for AML.…”