Issue Archive

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Locke and colleagues describe the safety and efficacy outcomes of axicabtagene ciloleucel for large B-cell lymphoma across racial and ethnic groups for 1290 standard-of-care patients in the Center for International Blood and Marrow Transplant Research registry and 275 patients treated in clinical trials. While consistency in survival and most safety outcomes were evident across groups, non-Hispanic Black patients had significantly lower response rates and progression-free survival in routine practice, potentially reflecting barriers to access.

Lenk and colleagues identified that 85% of cases of acute lymphoblastic leukemia (ALL) express interleukin-7 receptor (IL-7R). The authors reveal that blocking IL-7R signaling with lusvertikimab induces antibody-dependent cellular phagocytosis in patient-derived xenografts and shows in vivo efficacy, especially when combined with chemotherapy regimens. These preclinical data form the basis for future clinical trials of this approach.

Interleukin-1β (IL-1β) is secreted by the microenvironment in acute myeloid leukemia (AML) and can promote AML growth. Lin et al show that IL-1β upregulates Tousled-like kinases (TLKs) and antisilencing function-1B (ASF1B) in AML cells. Targeting TLK2 or ASF1B suppresses IL-1β–driven AML progression and may provide a future route to developing new therapies.

The innate immune system has memory capability with the adaption of functional responses by macrophages and neutrophils following an initial challenge. Guerrero and colleagues reveal a key role for granulocyte-macrophage colony-stimulating factor (GM-CSF) during the establishment of innate immune memory. Depending on the degree of differentiation in the myeloid series, GM-CSF induces 2 opposing memory programs, with macrophages derived from committed progenitors having a trained proinflammatory phenotype and macrophages derived from primitive progenitors showing a tolerized phenotype. The authors postulate that the twin effects provide a mechanism for temporal harmonization of immune memory.

Steady-state regulation of hepatic thrombopoietin (TPO) production is principally dictated by sensing of aged platelets by Ashwell-Morell receptors (AMRs) on hepatocytes. Using murine models, Sun et al identified hepatic Notch1 and platelet Delta-like 4 as key regulators of TPO production downstream of the AMRs, furthering our understanding of how we might therapeutically modulate TPO levels in patients with disorders of platelet number.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon but potentially fatal disorder with limited treatment options, particularly in the acute relapse setting. Muller et al demonstrate the pathological role of interleukin-1 (IL-1) in tissue damage during relapsed disease in patients and report the therapeutic potential of IL-1 receptor antagonist therapy in a murine model of TTP. This work suggests anakinra therapy should be evaluated in clinical studies.