ArticleBlood advances2022
4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Inflammation as a central driver in AML pathogenesis and therapy resistance.Science China. Life sciences · 2026Review
- Both soluble and cell surface CD137 expressed by Foxp3+ CD4 T cells restrain autoimmune diabetes.The Journal of experimental medicine · 2026Article
- Review
- CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.Nature communications · 2026Article
- Dysregulation of the Bone Marrow Microenvironment in Pediatric Tumors: The Role of Extracellular Vesicles in Acute Leukemias and Neuroblastoma.International journal of molecular sciences · 2025Review
- Crosstalk Between Extracellular Vesicles and Regulatory T Cells Across Cancers: From Interaction to Therapeutic Potential.International journal of nanomedicine · 2025Review
- Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target.Frontiers in immunology · 2025Review
- The biology of chronic myeloid leukemia: an overview of the new insights and biomarkers.Frontiers in oncology · 2025Review
- Immunosuppressive microenvironment in acute myeloid leukemia: overview, therapeutic targets and corresponding strategies.Annals of hematology · 2024Review
- Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics.Experimental & molecular medicine · 2024Review
- Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies.International journal of molecular sciences · 2024Review
- Article
- Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression.International journal of molecular sciences · 2024Review
- Extracellular vesicle-mediated communication between CD8Frontiers in immunology · 2024Review
- Immune interactions and regulation with CD39Frontiers in immunology · 2024Article
- The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways.Cell communication and signaling : CCS · 2023Review
- Dysfunctional subsets of CD39+ T cells, distinct from PD-1+, driven by leukemic extracellular vesicles in myeloid leukemias.Haematologica · 2023Article
- The extracellular vesicles targeting tumor microenvironment: a promising therapeutic strategy for melanoma.Frontiers in immunology · 2023Review
- Identification of DUSP7 as an RNA Marker for Prognostic Stratification in Acute Myeloid Leukemia: Evidence from Large Population Cohorts.Genetics research · 2023Article
- Extracellular vesicles in the Chronic Myeloid Leukemia scenario: an update about the shuttling of disease markers and therapeutic molecules.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic and acute myeloid leukemia evade immune system surveillance and induce immunosuppression by expanding proleukemic Foxp3+ regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, leukemia relapse, and shorter survival. However, mechanisms that promote Tregs in myeloid leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers of effector proleukemic Tregs. Using mouse model of leukemia-like disease, we found that Rab27a-dependent secretion of leukemic EVs promoted leukemia engraftment, which was associated with higher abundance of activated, immunosuppressive Tregs. Leukemic EVs attenuated mTOR-S6 and activated STAT5 signaling, as well as evoked significant transcriptomic changes in Tregs. We further identified specific effector signature of Tregs promoted by leukemic EVs. Leukemic EVs-driven Tregs were characterized by elevated expression of effector/tumor Treg markers CD39, CCR8, CD30, TNFR2, CCR4, TIGIT, and IL21R and included 2 distinct effector Treg (eTreg) subsets: CD30+CCR8hiTNFR2hi eTreg1 and CD39+TIGIThi eTreg2. Finally, we showed that costimulatory ligand 4-1BBL/CD137L, shuttled by leukemic EVs, promoted suppressive activity and effector phenotype of Tregs by regulating expression of receptors such as CD30 and TNFR2. Collectively, our work highlights the role of leukemic extracellular vesicles in stimulation of immunosuppressive Tregs and leukemia growth. We postulate that targeting of Rab27a-dependent secretion of leukemic EVs may be a viable therapeutic approach in myeloid neoplasms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.