Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia

Hyun, Shin Young; Na, Eun Jung; Jang, Ji Eun; Chung, Haerim; Kim, Soo Jeong; Kim, Jin Seok; Kong, Jee Hyun; Shim, Kwang Yong; Lee, Jong In; Min, Yoo Hong; Cheong, June Won

doi:10.1002/cam4.3360

Cited by 19 publications

(9 citation statements)

References 35 publications

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“…G-MDSC isolated from the blood of CML patients markedly suppressed normal donor T cell proliferation in vitro [ 121 ]. Functionally, also MDSC from bone marrow of AML patients exhibited high expression of Arg1 and IDO and efficiently suppressed CD8+ T cells’ effector function [ 194 ]. A recent study suggests that CD8+ T cell directed suppressive activity of MDSC in AML is based on VISTA (V-domain Ig suppressor of T cell activation) expression, as this suppressive effect was abrogated by silencing of VISTA in MDSC of AML patients [ 195 ].…”

Section: Mdsc and Macrophages In Myeloid Leukemiasmentioning

confidence: 99%

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Swatler

Turos-Korgul

Kozłowska

et al. 2021

Cancers

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Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. The following review focuses on main immunosuppressive features of myeloid leukemias. Firstly, factors derived directly from leukemic cells – inhibitory receptors, soluble factors and extracellular vesicles, are described. Further, we outline function, properties and origin of main immunosuppressive cells - regulatory T cells, myeloid derived suppressor cells and macrophages. Finally, we analyze interplay between recovery of effector immunity and therapeutic modalities, such as tyrosine kinase inhibitors and chemotherapy.

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Section: Mdsc and Macrophages In Myeloid Leukemiasmentioning

confidence: 99%

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Swatler

Turos-Korgul

Kozłowska

et al. 2021

Cancers

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“…A higher level of MDSCs in bone marrow may be regarded as a prognostic factor for AML ( 149 , 150 ). Alternatively, recent studies indicated that MDSC-like blasts from bone marrow mononuclear cells of AML patients could increase the levels of arginase-1 (ARG1) and inducible nitric oxide synthase (iNOS) that restrain CD8 + T-cell proliferation and induce T-cell apoptosis ( 151 ). Decreased MDSCs have enormously enhanced the TK/Flt3L gene-induced tumor-specific CD8 T-cell response to patients with gliomas ( 152 ).…”

Section: The Challenges Of Adoptive Tcr-t Cell Immunotherapy For Amlmentioning

confidence: 99%

Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges

Kang

Qiao

et al. 2022

Front. Oncol.

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The cytogenetic abnormalities and molecular mutations involved in acute myeloid leukemia (AML) lead to unique treatment challenges. Although adoptive T-cell therapies (ACT) such as chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the treatment of leukemias, especially B-cell malignancies, the optimal target surface antigen has yet to be discovered for AML. Alternatively, T-cell receptor (TCR)-redirected T cells can target intracellular antigens presented by HLA molecules, allowing the exploration of a broader territory of new therapeutic targets. Immunotherapy using adoptive transfer of WT1 antigen-specific TCR-T cells, for example, has had positive clinical successes in patients with AML. Nevertheless, AML can escape from immune system elimination by producing immunosuppressive factors or releasing several cytokines. This review presents recent advances of antigen-specific TCR-T cells in treating AML and discusses their challenges and future directions in clinical applications.

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“…Conversely, in an NK cell—AML-blasts co-culture system, Stringaris et al detected an increased level of IL-10 but not TGF-β, suggesting that inhibition of NK cells by AML blasts depends on IL-10 instead [ 58 ]. Myeloid-derived suppressor cells (MDSCs) are a distinct immature cell population that facilitates immune-evasive strategies [ 60 ]. Recently, MDSCs were shown to suppress the anti-leukemic activity of NK cells, mediated by IDO and prostaglandin-E2 (PGE2) and exosomes [ 61 ].…”

Section: Acute Myeloid Leukemia Harnesses the Immunological Microementioning

confidence: 99%

“…AML blasts are supposed to constitutively express IDO, nonetheless, the exact contribution to AML progression and immune tolerance remains to be elucidated [ 62 ]. Leukemic blasts induce MDSC proliferation and differentiation into tumor-associated macrophages, which further inhibit immunogenicity favoring their survival; thus driving leukemia progression resulting in deteriorated outcomes [ 60 , 63 , 64 ]. Deficient NK cell function can be traced back to weak expression of different activating natural cytotoxic receptors (NCRs) on AML-derived NK cells [ 54 , 55 , 56 ].…”

Section: Acute Myeloid Leukemia Harnesses the Immunological Microementioning

confidence: 99%

Redirecting the Immune Microenvironment in Acute Myeloid Leukemia

Sendker¹,

Reinhardt²,

Niktoreh³

2021

Cancers

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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.

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Immunosuppressive role of CD11b⁺CD33⁺HLA‐DR⁻ myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 19 publications

References 35 publications

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias

Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges

Redirecting the Immune Microenvironment in Acute Myeloid Leukemia

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