About this Research Topic
Acute myeloid leukemia (AML) accounts for 30% of all leukemias, with an estimated global incidence of 130,000 in 2018. Although numerous advances have been made in AML therapeutics, morbidity and mortality rates remain high. FDA approvals of immunotherapy for solid tumors in the last decade have sparked interest in studying immunotherapeutics in hematologic malignancies. Allogeneic stem cell transplant (allo-HCT) elicits graft-versus-leukemia effect, and numerous recent clinical trials have explored agents that engage one’s own immune system to combat myelodysplastic syndrome (MDS) and AML.
The current clinical trials pipeline of immunotherapies in AML includes macrophage checkpoint inhibitors, T cell checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells, bispecific T cell engagers (BiTEs), bispecific killer cell engagers (BiKEs), trispecific killer cell engagers (TriKEs), CAR-NK cells, and dual-affinity re-targeting (DART) molecules. There is an unmet need for new insights and solutions regarding how current investigational agents can be optimized in the upcoming months and years to harness autologous anti-cancer immunity more safely and effectively.
In this collection we are interested to understand the immunobiology of MDS and AML, with an emphasis on translational immunotherapeutics.
We would like to gather newer insights into the immunobiology of myeloid neoplasms. No immune-based targeted therapies are currently commercially available for patients with MDS or AML, despite various published laboratory research and clinical trials. The things that can be done to achieve this goal include:
• Identification of precision-based targets on MDS and AML cells
• Delineation of the immune-based microenvironment in the bone marrow and governs MDS and AML cell behavior
• Determination of the barriers to the clinical translation of novel immunotherapeutics
Recent advances in this field include translational efforts for leading pharmacologic agents, including the anti-TIM3 antibody sabatolimab, the anti-CD47 antibody magrolimab, and the anti-PD-1 agent nivolumab.
The scope of the research spans laboratory, translational, and clinical investigative efforts toward the advancement of the therapeutic armamentarium for MDS and AML. The scope includes studies of the anti-tumor effects of innate immunity (including neutrophils and macrophages) and adaptive immunity (including B cells and T cells). We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• Bone marrow microenvironment: the role of innate and adaptive immune responses within specific niches of bone marrow. Specifically, what immune effector responses are occurring in the arteriolar-pericyte niche, sinusoidal-megakaryocyte niche, and/or endosteal niche?
• T cell checkpoints: CTLA-4 checkpoint, PD-1 checkpoint, and TIM3 checkpoint. Specifically, what is the role of inhibitory antibodies against these checkpoints?
• Macrophage checkpoints: specifically, CD47/SIRPalpha checkpoint and how targeting this axis can lead to more effective innate immunity against MDS and AML cells
• Molecular target validation: surveying the cell surface proteome to identify targets and vulnerabilities in AML cells
• Immunologic cell surface proteome in MDS and AML: the cell-surface crosstalk between adaptive immunity and AML cells
We welcome the submission of Original Research, Review, Mini Review, and perspective articles.
Please note, manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic editor Shyam A. Patel serves on the Acute Myeloid Leukemia advisory board for Bristol Myers Squibb and served on the Multiple Myeloma advisory board for Pfizer. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
The current clinical trials pipeline of immunotherapies in AML includes macrophage checkpoint inhibitors, T cell checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells, bispecific T cell engagers (BiTEs), bispecific killer cell engagers (BiKEs), trispecific killer cell engagers (TriKEs), CAR-NK cells, and dual-affinity re-targeting (DART) molecules. There is an unmet need for new insights and solutions regarding how current investigational agents can be optimized in the upcoming months and years to harness autologous anti-cancer immunity more safely and effectively.
In this collection we are interested to understand the immunobiology of MDS and AML, with an emphasis on translational immunotherapeutics.
We would like to gather newer insights into the immunobiology of myeloid neoplasms. No immune-based targeted therapies are currently commercially available for patients with MDS or AML, despite various published laboratory research and clinical trials. The things that can be done to achieve this goal include:
• Identification of precision-based targets on MDS and AML cells
• Delineation of the immune-based microenvironment in the bone marrow and governs MDS and AML cell behavior
• Determination of the barriers to the clinical translation of novel immunotherapeutics
Recent advances in this field include translational efforts for leading pharmacologic agents, including the anti-TIM3 antibody sabatolimab, the anti-CD47 antibody magrolimab, and the anti-PD-1 agent nivolumab.
The scope of the research spans laboratory, translational, and clinical investigative efforts toward the advancement of the therapeutic armamentarium for MDS and AML. The scope includes studies of the anti-tumor effects of innate immunity (including neutrophils and macrophages) and adaptive immunity (including B cells and T cells). We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• Bone marrow microenvironment: the role of innate and adaptive immune responses within specific niches of bone marrow. Specifically, what immune effector responses are occurring in the arteriolar-pericyte niche, sinusoidal-megakaryocyte niche, and/or endosteal niche?
• T cell checkpoints: CTLA-4 checkpoint, PD-1 checkpoint, and TIM3 checkpoint. Specifically, what is the role of inhibitory antibodies against these checkpoints?
• Macrophage checkpoints: specifically, CD47/SIRPalpha checkpoint and how targeting this axis can lead to more effective innate immunity against MDS and AML cells
• Molecular target validation: surveying the cell surface proteome to identify targets and vulnerabilities in AML cells
• Immunologic cell surface proteome in MDS and AML: the cell-surface crosstalk between adaptive immunity and AML cells
We welcome the submission of Original Research, Review, Mini Review, and perspective articles.
Please note, manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic editor Shyam A. Patel serves on the Acute Myeloid Leukemia advisory board for Bristol Myers Squibb and served on the Multiple Myeloma advisory board for Pfizer. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Keywords: acute myeloid leukemia; checkpoint blockade; immunotherapy; microenvironment; myelodysplastic syndrome; targeted therapies
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
