Advances in Personalized Therapy: Co-targeting Intracellular Immune checkpoints in Controlling Acute Myeloid Leukemia

2021 ◽  
pp. 108-151
Author(s):  
Sunil Kumar ◽  
Muhammad Umer Ashraf ◽  
Ashok Kumar Aman ◽  
Yong-Soo Bae
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Personalized Therapy ◽  
Immune Checkpoints ◽  
Acute Myeloid

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

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.

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 Phenotypical heterogeneity of acute myeloid leukemia in the elderly: a clue for a personalized therapy?

2020 ◽  
Vol 61 (5) ◽  
pp. 1234-1237
Author(s):  
Giacomo Andreani ◽  
Sofia Camerlo ◽  
Marisa Pautasso ◽  
Matteo Dragani ◽  
Giovanna Carrà ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
The Elderly ◽  
Personalized Therapy ◽  
Acute Myeloid

scholarly journals Personalized Therapy for Acute Myeloid Leukemia

2013 ◽  
Vol 3 (12) ◽  
pp. 1336-1338 ◽  
Author(s):  
Christopher S. Hourigan ◽  
Judith E. Karp
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Personalized Therapy ◽  
Acute Myeloid

scholarly journals New drugs for acute myeloid leukemia inspired by genomics and when to use them

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Daniel A. Pollyea
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapies ◽  
Myeloid Leukemia ◽  
Clinical Care ◽  
Personalized Therapy ◽  
New Drugs ◽  
Targeted Sequencing ◽  
Minimal Toxicity ◽  
New Treatment ◽  
Acute Myeloid

Abstract We are several years into the “postdiscovery” era in acute myeloid leukemia (AML) thanks to extensive work involving the sequencing of genomes and exomes of countless patients, which has led to routine comprehensive targeted sequencing in clinical care. The ability to unlock the molecular underpinnings of each patient’s disease was supposed to usher in a new treatment era in which each patient was assigned, based on her mutational profile, a personalized cocktail of targeted therapies that would snuff the disease into submission with minimal toxicity. Whether we have fully realized the promise of personalized therapy in AML is unclear. Here, I review those new drugs that have been inspired by genomics, discuss others that might be possible and their potential roles, and consider whether the ability to target genomic mutations in a personalized manner constitutes the future of AML therapeutics or is representative of an era that has already passed.

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