The immune checkpoints Cytotoxic T lymphocyte antigen‐4 and Lymphocyte activation gene‐3 expression is up‐regulated in acute myeloid leukemia

HLA ◽  
2020 ◽  
Vol 96 (1) ◽  
pp. 3-12
Author(s):  
Sara M. Radwan ◽  
Nooran S. Elleboudy ◽  
Nermeen A. Nabih ◽  
Amany M. Kamal
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Lymphocyte ◽  
Myeloid Leukemia ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Activation ◽  
Immune Checkpoints ◽  
Lymphocyte Antigen ◽  
Lymphocyte Activation Gene ◽  
Acute Myeloid

scholarly journals Targeting Immune Signaling Checkpoints in Acute Myeloid Leukemia

2019 ◽  
Vol 8 (2) ◽  
pp. 236 ◽  
Author(s):  
Krzysztof Giannopoulos
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Negative Control ◽  
Immune Checkpoints ◽  
Hematopoietic Stem ◽  
Acute Myeloid

The modest successes of targeted therapies along with the curative effects of allogeneic hematopoietic stem cell transplantation (alloHSCT) in acute myeloid leukemia (AML) stimulate the development of new immunotherapies. One of the promising methods of immunotherapy is the activation of immune response by the targeting of negative control checkpoints. The two best-known inhibitory immune checkpoints are cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 receptor (PD-1). In AML, PD-1 expression is observed in T-cell subpopulations, including T regulatory lymphocytes. Increased PD-1 expression on CD8+ T lymphocytes may be one of the factors leading to dysfunction of cytotoxic T cells and inhibition of the immune response during the progressive course of AML. Upregulation of checkpoint molecules was observed after alloHSCT and therapy with hypomethylating agents, pointing to a potential clinical application in these settings. Encouraging results from recent clinical trials (a response rate above 50% in a relapsed setting) justify further clinical use. The most common clinical trials employ two PD-1 inhibitors (nivolumab and pembrolizumab) and two anti-PD-L1 (programmed death-ligand 1) monoclonal antibodies (atezolizumab and durvalumab). Several other inhibitors are under development or in early phases of clinical trials. The results of these clinical trials are awaited with great interest in, as they may allow for the established use of checkpoint inhibitors in the treatment of AML.

scholarly journals Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Francesco Romano ◽  
Antonino Giulio Giannone ◽  
Sergio Siragusa ◽  
Rossana Porcasi ◽  
Ada Maria Florena
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Escape ◽  
Medical Community ◽  
Immune Checkpoints ◽  
Bone Marrow Biopsies ◽  
Underlying Mechanisms ◽  
Acute Myeloid

tumor immunotherapy is a rapidly evolving field. The discovery of the ability of neoplasms to evade the immune response has shifted the attention of the medical community to the underlying mechanisms of the immune response to tumors, highlighting the importance of so-called immune check points, including CTLA4, TIM-3 and PD-1.  an immune escape mechanism is the activation of the immune checkpoint pathway that contributes to the creation of an immunosuppressive microenvironment and therefore to tumor proliferation.although immune checkpoints have been extensively investigated in solid tumors, the same is not true for hematologic neoplasms, particularly for myeloid malignancies. our study is based on the evaluation of the activation of the PD-1 and PD-L1 pathway in the context of the bone marrow tumor microenvironment of patients with acute myeloid leukemia. To do so we evaluated  34 bone marrow biopsies of patients with acute myeloid leukemia comparing them to 10 controls using immunohistochemical methods.

scholarly journals Immune Checkpoints of CD8+ T Cells in Acute Myeloid Leukemia

2018 ◽  
Vol 12 (1) ◽  
Author(s):  
Yang J ◽  
Liu G ◽  
Zhou M ◽  
Cheng J ◽  
Chen Q ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Cd8 T Cells ◽  
Myeloid Leukemia ◽  
Immune Checkpoints ◽  
Acute Myeloid

3103 – OPTIMAL COMBINATION OF IMMUNE CHECKPOINTS PREDICTS ADVERSE OUTCOMES IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

2020 ◽  
Vol 88 ◽  
pp. S70
Author(s):  
Yangqiu Li ◽  
Cunte Chen ◽  
Chaofeng Liang ◽  
Shunqing Wang ◽  
Chi Leong Chio ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Adverse Outcomes ◽  
Optimal Combination ◽  
Immune Checkpoints ◽  
Acute Myeloid

scholarly journals Impact of Bone Marrow miR-21 Expression on Acute Myeloid Leukemia T Lymphocyte Fragility and Dysfunction

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2053
Author(s):  
Douâa Moussa Agha ◽  
Redouane Rouas ◽  
Mehdi Najar ◽  
Fatima Bouhtit ◽  
Hussein Fayyad-Kazan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Myeloid Leukemia ◽  
Myeloid Cell ◽  
Leukemic Cells ◽  
Hematopoietic Malignancy ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy in which antitumor immunity is impaired. The therapeutic management of AML requires understanding the mechanisms involved in the fragility and immune dysfunction of AML T lymphocytes. Methods: In this study, T lymphocytes from healthy donors (HD) and AML patients were used. Extracellular vesicles (EVs) from leukemic cells were screened for their microRNA content and impact on T lymphocytes. Flow cytometry, transcriptomic as well as lentiviral transduction techniques were used to carry out the research. Results: We observed increased cell death of T lymphocytes from AML patients. EVs from leukemia myeloid cell lines harbored several miRNAs, including miR-21, and were able to induce T lymphocyte death. Compared to that in HD, miR-21 was overexpressed in both the bone marrow fluid and infiltrating T lymphocytes of AML patients. MiR-21 induces T lymphocyte cell death by upregulating proapoptotic gene expression. It also increases the immunosuppressive profile of T lymphocytes by upregulating the IL13, IL4, IL10, and FoxP3 genes. Conclusions: Our results demonstrate that miR-21 plays a significant role in AML T lymphocyte dysfunction and apoptosis. Targeting miR-21 may be a novel approach to restore the efficacy of the immune response against AML.

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