CARving the Path to Allogeneic CAR T Cell Therapy in Acute Myeloid Leukemia

Pasvolsky, Oren; Daher, May; Alatrash, Gheath; Marín, David; Daver, Naval; Ravandi, Farhad; Rezvani, Katy; Shpall, Elizabeth J.; Kebriaei, Partow

doi:10.3389/fonc.2021.800110

Cited by 9 publications

(8 citation statements)

References 88 publications

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“…In AML, the immunomodulatory network in the BMM is an important factor promoting cancer progression [25]. Tese regulatory networks include chemotactic cytokines, immunostimulatory molecules, MHC, and receptors.…”

Section: Discussionmentioning

confidence: 99%

CD86 Is Associated with Immune Infiltration and Immunotherapy Signatures in AML and Promotes Its Progression

Zhang

Chen

et al. 2023

Journal of Oncology

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Background. Cluster of differentiation 86 (CD86), also known as B7-2, is a molecule expressed on antigen-presenting cells that provides the costimulatory signals required for T cell activation and survival. CD86 binds to two ligands on the surface of T cells: the antigen CD28 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). By binding to CD28, CD86—together with CD80—promotes the participation of T cells in the antigen presentation process. However, the interrelationships among CD86, immunotherapy, and immune infiltration in acute myeloid leukemia (AML) are unclear. Methods. The immunological effects of CD86 in various cancers (including on chemokines, immunostimulators, MHC, and receptors) were evaluated through a pan-cancer analysis using TCGA and GEO databases. The relationship between CD86 expression and mononucleotide variation, gene copy number variation, methylation, immune checkpoint blockers (ICBs), and T-cell inflammation score in AML was subsequently examined. ESTIMATE and limma packages were used to identify genes at the intersection of CD86 with StromalScore and ImmuneScore. Subsequently, GO/KEGG and PPI network analyses were performed. The immune risk score (IRS) model was constructed, and the validation set was used for verification. The predictive value was compared with the TIDE score. Results. CD86 was overexpressed in many cancers, and its overexpression was associated with a poor prognosis. CD86 expression was positively correlated with the expression of CTLA4, PDCD1LG2, IDO1, HAVCR2, and other genes and negatively correlated with CD86 methylation. The expression of CD86 in AML cell lines was detected by QRT-PCR and Western blot, and the results showed that CD86 was overexpressed in AML cell lines. Immune infiltration assays showed that CD86 expression was positively correlated with CD8 T cell, Dendritic cell, macrophage, NK cell, and Th1_cell and also with immune examination site, immune regulation, immunotherapy response, and TIICs. ssGSEA showed that CD86 was enriched in immune-related pathways, and CD86 expression was correlated with mutations in the genes RB1, ERBB2, and FANCC, which are associated with responses to radiotherapy and chemotherapy. The IRS score performed better than the TIDE website score. Conclusion. CD86 appears to participate in immune invasion in AML and is an important player in the tumor microenvironment in this malignancy. At the same time, the IRS score developed by us has a good effect and may provide some support for the diagnosis of AML. Thus, CD86 may serve as a potential target for AML immunotherapy.

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Section: Discussionmentioning

confidence: 99%

CD86 Is Associated with Immune Infiltration and Immunotherapy Signatures in AML and Promotes Its Progression

Zhang

Chen

et al. 2023

Journal of Oncology

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“…Chimeric Antigen Receptor T-cell (CAR-T) therapy, involves genetically engineering T cells to express chimeric antigen receptors, enabling them to recognize and eliminate tumor cells ( 111 ). However, only limited efficacy of CAR-T therapy targeting CD33, CD123 in AML have been observed in clinical trials ( 112 ).…”

Section: Expanding Therapeutic Opportunitiesmentioning

confidence: 99%

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Zhou,

Chng

2024

Front. Oncol.

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Acute myeloid leukemia (AML) is a complex and heterogeneous group of aggressive hematopoietic stem cell disease. The presence of diverse and functionally distinct populations of leukemia cells within the same patient’s bone marrow or blood poses a significant challenge in diagnosing and treating AML. A substantial proportion of AML patients demonstrate resistance to induction chemotherapy and a grim prognosis upon relapse. The rapid advance in next generation sequencing technologies, such as single-cell RNA-sequencing (scRNA-seq), has revolutionized our understanding of AML pathogenesis by enabling high-resolution interrogation of the cellular heterogeneity in the AML ecosystem, and their transcriptional signatures at a single-cell level. New studies have successfully characterized the inextricably intertwined interactions among AML cells, immune cells and bone marrow microenvironment and their contributions to the AML development, therapeutic resistance and relapse. These findings have deepened and broadened our understanding the complexity and heterogeneity of AML, which are difficult to detect with bulk RNA-seq. This review encapsulates the burgeoning body of knowledge generated through scRNA-seq, providing the novel insights and discoveries it has unveiled in AML biology. Furthermore, we discuss the potential implications of scRNA-seq in therapeutic opportunities, focusing on immunotherapy. Finally, we highlight the current limitations and future direction of scRNA-seq in the field.

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“…Post-allo-HSCT relapse has become the major cause of treatment failure and is associated with a dismal prognosis[ 134 ]. Post-allo-HSCT relapse may come from normal donor cells, known as donor cell leukemia (DCL; rare, 0.12% to 5.0%), or recipient cells (most cases)[ 135 , 136 , 137 ]. Despite the remarkable advancement in allo-HSCT technology in recent years, there has been little progress on how to reduce post-allo-HSCT relapse or improve the survival of relapsed patients.…”

Section: Mechanism Of Post-transplant Leukemia Relapsementioning

confidence: 99%

“…Another potential future strategy is to target AML-associated, e.g. , WT1 or PR1, rather than AML-specific antigens using peptide vaccines[ 137 , 190 , 191 ]. However, at present, allo-HSCT remains the standard of care for individuals diagnosed with AML and who display evidence of intermediate or unfavorable risk, and the potential benefits of CAR-T cell therapy in conjunction with pharmacological agents and/or allo-HSCT in the management of AML remains to be decided in future studies[ 192 ].…”

Section: Intervention and Treatment Strategies For Post-allo-hsct Rel...mentioning

confidence: 99%

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

Chen¹,

Li²,

Xu³

et al. 2023

World J Clin Cases

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As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and post-transplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

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CARving the Path to Allogeneic CAR T Cell Therapy in Acute Myeloid Leukemia

Cited by 9 publications

References 88 publications

CD86 Is Associated with Immune Infiltration and Immunotherapy Signatures in AML and Promotes Its Progression

CD86 Is Associated with Immune Infiltration and Immunotherapy Signatures in AML and Promotes Its Progression

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

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