Soluble HLA-G: A novel marker in acute myeloid leukemia patients

Hamed, Nahla A M; Halawani, Nabil El; Nafea, Dalia; Ahmed, Mohamed Abdel Rahman; Kasber, Ahmed

doi:10.5530/ami.2017.4.10

Cited by 3 publications

(3 citation statements)

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“…While W6/32 is a pan-HLA-I antibody, TP25.99 is not ( Figure 1 ) [ 63 , 64 ]. This setup thus overlooked sHLA-G which was later demonstrated to be elevated in AML patients [ 54 ]. During the first international workshop on sHLA antigens, a fairly good correlation between sHLA-I assays from different laboratories was found despite the use of different antibodies and/or protocols [ 65 ].…”

Section: Shla In Malignanciesmentioning

confidence: 99%

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

2020

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Human leukocyte antigen (HLA) molecules are essential for anti-tumor immunity, as they display tumor-derived peptides to drive tumor eradication by cytotoxic T lymphocytes. HLA molecules are primarily studied as peptide-loaded complexes on cell membranes (mHLA) and much less attention is given to their secretion as soluble HLA–peptide complexes (sHLA) into bodily fluids. Yet sHLA levels are altered in various pathologies including cancer, and are thus of high interest as biomarkers. Disconcordance in results across studies, however, hampers interpretation and generalization of the relationship between sHLA levels and cancer presence, thereby impairing its use as a biomarker. Furthermore, the question remains to what extent sHLA complexes exert immunomodulatory effects and whether shifts in sHLA levels contribute to disease or are only a consequence of disease. sHLA complexes can also bear tumor-derived peptides and recent advancements in mass spectrometry now permit closer sHLA peptide cargo analysis. sHLA peptide cargo may represent a “liquid biopsy” that could facilitate the use of sHLA for cancer diagnosis and target identification for therapeutic vaccination. This review aims to outline the contradictory and unexplored aspects of sHLA and to provide direction on how the full potential of sHLA as a quantitative and qualitative biomarker can be exploited.

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Section: Shla In Malignanciesmentioning

confidence: 99%

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

2020

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“…It is thought that tumor cells are protected from NK cells and cytotoxic T lymphocytes by expressing HLA-G, which is a tumor-induced immune escape mechanism. Patients with relapsed AML had significantly higher levels of soluble HLA-G than controls [ 43 ]. Moreover, recent studies revealed that the increased mRNA levels of KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL1, and KIR3DL2 are significantly associated with poor prognosis and overall survival (OS) for AML patients.…”

Section: Bone Marrow Microenvironment Cells In Aml: Immune Checkpoint...mentioning

confidence: 99%

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways

Bakhtiyari,

Liaghat,

Aziziyan

et al. 2023

Cell Commun Signal

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Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML.

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“…It has been shown that the soluble isoforms of HLA-G are increased in distinct AML samples, especially in monocytic lineages, following interferon (IFN)-gamma and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) stimulation [ 23 , 24 ]. In addition, different isoforms of HLA-G have been reported to be secreted or expressed by leukemic cells associated with a higher blast percentage in bone marrow, decreased T cell number, and relapses, which may indicate HLA-G as an additional strategy for AML blasts to evade immune surveillance [ 25 , 26 ]. However, the clinical impact of HLA-G in leukemogenesis appears to be controversial as opposing results do not confirm the clinical implications of HLA-G [ 27 ].…”

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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Soluble HLA-G: A novel marker in acute myeloid leukemia patients

Cited by 3 publications

References 0 publications

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways

Redirecting the Immune Microenvironment in Acute Myeloid Leukemia

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