Contribution of <scp>CD</scp>39 to the immunosuppressive microenvironment of acute myeloid leukaemia at diagnosis

Dulphy, Nicolas; Henry, Guylaine; Hémon, Patrice; Khaznadar, Zena; Dombret, Hervé; Boissel, Nicolas; Bensussan, Armand; Toubert, Antoine

doi:10.1111/bjh.12774

Cited by 33 publications

(21 citation statements)

References 10 publications

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“…To escape the allogeneic immune response, some leukemia subtypes may produce enzymes that change the metabolism. Examples include indoleamine 2,3-dioxygenase-1 (IDO1) [46], arginase [47], CD39 [48], and CD73 [49]. The enzyme CD73 converts adenosine-monophosphate into adenosine, a metabolite that inhibits the function of T cells and dendritic cells.…”

Section: Biology Of Relapsementioning

confidence: 99%

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Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

Zeiser

Beelen

Bethge³

et al. 2019

Biology of Blood and Marrow Transplantation

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The curative potential of allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) relies mainly on the graft-versus-leukemia effect. Relapse after allo-HCT occurs in a considerable proportion of patients and has a dismal prognosis, with still very limited curative potential. This review provides an overview of the established and evolving approaches to preventing or treating relapse of AML and MDS after allo-HCT, in the context of novel insight into the biology of relapse. Established prophylactic measures to prevent relapse include optimized conditioning and graft-versushost disease (GVHD) prophylaxis, as well as donor lymphocyte infusion (DLI) for high-risk patients; novel immunomodulatory interventions and maintenance approaches are still experimental. Improved diagnostics can detect persistent or recurring disease at a molecular level, enabling early preemptive interventions. Established options include hypomethylating agents and DLI. Standard treatments for hematologic relapse include chemotherapy, cessation of immunosuppressive treatment, and DLI. Experimental approaches include molecular targeted therapies, novel immunomodulatory treatments, and second allo-HCT. For all interventions, the potential risks, including occurrence of GVHD, must be weighed against the benefits individually in each patient. Concurrently, prevention and treatment of relapse after allo-HCT remain challenging and unmet medical needs.

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Section: Biology Of Relapsementioning

confidence: 99%

“…The A2aR inhibitors are mostly combined with immune checkpoint inhibitors. The enzyme CD39 can interfere with immune activation in AML at primary diagnosis [48].…”

Section: Biology Of Relapsementioning

confidence: 99%

Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

Zeiser

Beelen

Bethge³

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Thus, CD39 and CD73 promote an anti-inflammatory microenvironment through the enhanced production of adenosine. Using CD73-defective mice it has been demonstrated that, after allo-HSCT, low CD73 activity enhances leukemia cell recognition and destruction by alloreactive T cells [75,76].…”

Section: Other Mechanismsmentioning

confidence: 99%

Immune Escape after Hematopoietic Stem Cell Transplantation (HSCT): From Mechanisms to Novel Therapies

Bernasconi

Borsani

2019

Cancers

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Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Recent advances in understanding its molecular basis have opened the way to new therapeutic strategies, including targeted therapies. However, despite an improvement in prognosis it has been documented in recent years (especially in younger patients) that allogenic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment in AML and the first therapeutic option for high-risk patients. After allo-HSCT, relapse is still a major complication, and is observed in about 50% of patients. Current evidence suggests that relapse is not due to clonal evolution, but instead to the ability of the AML cell population to escape immune control by a variety of mechanisms including the altered expression of HLA-molecules, production of anti-inflammatory cytokines, relevant metabolic changes and expression of immune checkpoint (ICP) inhibitors capable of “switching-off” the immune response against leukemic cells. Here, we review the main mechanisms of immune escape and identify potential strategies to overcome these mechanisms.

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“…Mechanistically, Tregs exhibit increased suppression compared with control healthy donor Tregs and appear to be induced by direct contact with AML blasts (6,45,46). Leukemia cells may produce adenosine via expression of ectonucleotides CD39 and CD73 thus suppressing effector T cells and supporting Treg function (47). Furthermore, MDSCs are increased in peripheral blood from patients with AML.…”

Section: Suppressive Cellular Microenvironmentmentioning

confidence: 99%

Novel Approaches to Acute Myeloid Leukemia Immunotherapy

Beyar-Katz

Gill

2018

Clinical Cancer Research

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Acute myeloid leukemia (AML) is a rapidly progressive, poor-prognosis malignancy arising from hematopoietic stem/progenitor cells. The long history of successful use of allogeneic hematopoietic cell transplantation (alloHCT) in AML indicates that this disease is immunoresponsive, leading to optimism that novel immunotherapies such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors will generate meaningful disease control. However, emerging data on the immunoevasive tactics employed by AML blasts at diagnosis and at relapse indicate that optimism must be tempered by an understanding of this essential paradox. Furthermore, AML has a low mutational burden, thus presenting few neoantigens for attack by autologous T cells, even after attempted reversal of inhibitory receptor/ligand interactions. In this review, we outline the known AML targets, explore immune evasion mechanisms, and describe recent data and current clinical trials of single and combination immunotherapies. .

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Contribution of CD39 to the immunosuppressive microenvironment of acute myeloid leukaemia at diagnosis

Cited by 33 publications

References 10 publications

Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

Immune Escape after Hematopoietic Stem Cell Transplantation (HSCT): From Mechanisms to Novel Therapies

Novel Approaches to Acute Myeloid Leukemia Immunotherapy

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