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Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches.

ABSTRACT: Acute myeloid leukemias (AML) comprise a wide array of different entities, which have in common a rapid expansion of myeloid blast cells leading to displacement of normal hematopoietic cells and also disruption of the microenvironment in the bone marrow niches. Based on an insight into the complex cellular interactions in the bone marrow niches in non-neoplastic conditions in general, this review delineates the complex relationship between leukemic cells and reactive cells of the tumor microenvironment (TME) in AML. A special focus is directed on niche cells and various T-cell subsets as these also provide a potential therapeutic rationale considering e.g. immunomodulation. The TME of AML on the one hand plays a vital role for sustaining and promoting leukemogenesis but - on the other hand - it also has adverse effects on abnormal blasts developing into overt leukemia hindering their proliferation and potentially removing such cells. Thus, leukemic cells need to and develop strategies in order to manipulate the TME. Interference with those strategies might be of particular therapeutic potential since mechanisms of resistance related to tumor cell plasticity do not apply to it.

SUBMITTER: Menter T

PROVIDER: S-EPMC8901718 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches.

Menter Thomas T Tzankov Alexandar A

Frontiers in immunology 20220222

Acute myeloid leukemias (AML) comprise a wide array of different entities, which have in common a rapid expansion of myeloid blast cells leading to displacement of normal hematopoietic cells and also disruption of the microenvironment in the bone marrow niches. Based on an insight into the complex cellular interactions in the bone marrow niches in non-neoplastic conditions in general, this review delineates the complex relationship between leukemic cells and reactive cells of the tumor microenvi ...[more]

PMID: 35273598

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Project description:Simple Summary Despite remarkable progress in the outcome of childhood acute myeloid leukemia (AML), risk of relapse and refractory diseases remains high. Treatment of the chemo-refractory disease is restricted by dose-limiting therapy-related toxicities which necessitate alternative tolerable efficient therapeutic modalities. By disrupting its immune environment, leukemic blasts are known to gain the ability to evade immune surveillance and promote disease progression; therefore, many efforts have been made to redirect the immune system against malignant blasts. Deeper knowledge about immunologic alterations has paved the way to the discovery and development of novel targeted therapeutic concepts, which specifically override the immune evasion mechanisms to eradicate leukemic blasts. Herein, we review innovative immunotherapeutic strategies and their mechanisms of action in pediatric AML. Abstract Acute myeloid leukemia is a life-threatening malignant disorder arising in a complex and dysregulated microenvironment that, in part, promotes the leukemogenesis. Treatment of relapsed and refractory AML, despite the current overall success rates in management of pediatric AML, remains a challenge with limited options considering the heavy but unsuccessful pretreatments in these patients. For relapsed/refractory (R/R) patients, hematopoietic stem cell transplantation (HSCT) following ablative chemotherapy presents the only opportunity to cure AML. Even though in some cases immune-mediated graft-versus-leukemia (GvL) effect has been proven to efficiently eradicate leukemic blasts, the immune- and chemotherapy-related toxicities and adverse effects considerably restrict the feasibility and therapeutic power. Thus, immunotherapy presents a potent tool against acute leukemia but needs to be engineered to function more specifically and with decreased toxicity. To identify innovative immunotherapeutic approaches, sound knowledge concerning immune-evasive strategies of AML blasts and the clinical impact of an immune-privileged microenvironment is indispensable. Based on our knowledge to date, several promising immunotherapies are under clinical evaluation and further innovative approaches are on their way. In this review, we first focus on immunological dysregulations contributing to leukemogenesis and progression in AML. Second, we highlight the most promising therapeutic targets for redirecting the leukemic immunosuppressive microenvironment into a highly immunogenic environment again capable of anti-leukemic immune surveillance.

Dataset Information

Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches.

Publications

Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches.

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