Exosome: From leukemia progression to a novel therapeutic approach in leukemia treatment

Gholipour, Elham; Sarvarian, Parisa; Samadi, Parisa; Talebi, Mehdi; Movassaghpour, Aliakbar; Motavalli, Roza; Hojjat‐Farsangi, Mohammad; Yousefi, Mehdi

doi:10.1002/biof.1669

Cited by 11 publications

(6 citation statements)

References 187 publications

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“…Exosomes derived from tumor cells, including leukemia cells, are a rich source of tumor antigens; these antigens originate from parental cells and reflect the tumor content and activities of these parental cells [27,28]. TEX carrying tumor-associated antigens can act as potent inducers of the immune response [29].…”

Section: Discussionmentioning

confidence: 99%

Enhancing the anti-leukemia immunity of leukemia-derived exosome-based vaccine by downregulation of PD-L1 expression

Huang¹,

Z²,

Zhang³

et al. 2021

Preprint

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Cell-released nanovesicles can induce anti-leukemia immunity. Leukemia cell-derived exosomes (LEXs) are promising anti-tumor vaccine components for cancer immunotherapy. Nonetheless, LEX-based vaccines show modest potency in vivo, likely due to the presence of immunosuppressive PD-L1 proteins in the exosomes. We hypothesized that targeting exosomal PD-L1 could optimize LEX-based vaccines. To test this hypothesis, we compared the capacity of exosomes derived from PD-L1-silenced leukemia cells (LEXPD-L1si) and non-modified exosomes to induce anti-leukemia immunity.Lentivirus-mediated PD-L1 shRNA was used to downregulate PD-L1 expression in parental leukemia cells and LEXs. LEXPD-L1si were characterized by electron microscopy, western blotting, and flow cytometry, and their anti-leukemia immune effects were tested on immune cells and in animal models.In the present study, lentivirus-mediated PD-L1 shRNA successfully downregulated PD-L1 expression in parental leukemia cells and in LEXs. LEXPD-L1si induced better DC maturation and subsequently enhanced T-cell activation, as compared with non-modified LEXs. Consistently, immunization with LEXPD-L1si induced greater T-cell proliferation and Th1 cytokine release. LEXPD-L1si was a more potent inducer of antigen-specific cytotoxic lymphocyte (CTL) response. Finally, we vaccinated DBA/2 mice with exosome formulations to test their ability to induce both protective and therapeutic anti-tumor CTL responses in vivo. Vaccination with LEXPD-L1si strongly inhibited tumor growth and prolonged survival. Downregulation of exosomal PD-L1 expression in LEXs effectively induce more potent anti-leukemia immunity. Therefore our strategy for optimizing LEX-based vaccine has a potential application in leukemia immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Enhancing the anti-leukemia immunity of leukemia-derived exosome-based vaccine by downregulation of PD-L1 expression

Huang¹,

Z²,

Zhang³

et al. 2021

Preprint

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“…Several studies demonstrated the key role of exosomes in haematological malignancies 31,32 . Recent evidence supports the role of leukaemia‐derived exosomes (LEXs) in cancer growth, as well as the treatment of human haematological diseases.…”

Section: Introductionmentioning

confidence: 91%

“…Several studies demonstrated the key role of exosomes in haematological malignancies. 31,32 Recent evidence supports the role of leukaemia-derived exosomes (LEXs) in cancer growth, as well as the treatment of human haematological diseases. Leukaemia-derived exosomes interacting with B and T cells, monocytes, natural killer (NK) cells and granulocytes create an immunoinhibitory environment to help the escape of leukaemia cells from the immune responses.…”

Section: Introductionmentioning

confidence: 99%

Paediatric pre‐B acute lymphoblastic leukaemia‐derived exosomes regulate immune function in human T cells

Gholipour

Kahroba

Soltani

et al. 2022

J Cellular Molecular Medi

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Exosomes derived from solid tumour cells are involved in immune suppression, angiogenesis and metastasis; however, the role of leukaemia‐derived exosomes has less been investigated. Hence, changes in immune response‐related genes and human T cells apoptosis co‐incubated with exosomes isolated from patients' pre‐B cell acute lymphoblastic leukaemia were evaluated in this in vitro study. Vein blood sample was obtained from each newly diagnosed acute lymphoblastic leukaemia (ALL) patient prior any therapy. ALL serum exosomes were isolated by ultrafiltration and characterized using Western blotting and transmission electron microscopy. Exosomes were then co‐incubated with T lymphocytes and the gene expressions, as well as functions of human T cells were quantified by qRT‐PCR. Apoptosis and caspase‐3 and caspase‐9 protein expression were also evaluated by flowcytometry and Western blotting analysis, respectively. Exosomes isolated from ALL patients affected T lymphocytes and elevated the apoptosis. Moreover, these exosomes altered the T cells profile into regulatory type by increasing the expression of FOXP3 and Tregs‐related cytokines, including TGF‐B and IL‐10. The expression level of Th17‐related transcription factors (RoRγt) and interleukins (IL‐17 and IL‐23) decreased after this treatment. According to our findings, exosomes derived from ALL patients' sera carry immunosuppressive molecules, indicating the possible effect of exosomes as liquid biomarkers for cancer staging.

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“…As reported above, circulating sEVs cargo has been deeply analyzed to detect potential shuttled leukemia markers ( 41 ). Despite the recurring availability of leukemic cells in myeloid leukemias in either BM and/or PB, many groups have conducted studies aiming to improve the sensitivity of the analysis and to reduce the number of invasive and painful BM biopsy ( 42 ).…”

Section: Sevs As Shuttle Of CML Markersmentioning

confidence: 99%

Extracellular vesicles in the Chronic Myeloid Leukemia scenario: an update about the shuttling of disease markers and therapeutic molecules

Bernardi,

Mulas,

Mutti

et al. 2024

Front. Oncol.

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Extracellular vesicles (EVs) are various sets of cell-derived membranous structures containing lipids, nucleic acids, and proteins secreted by both eukaryotic and prokaryotic cells. It is now well recognized that EVs are key intercellular communication mediators, allowing the functional transfer of bioactive chemicals from one cell to another in both healthy and pathological pathways. It is evident that the condition of the producer cells heavily influences the composition of EVs. Hence, phenotypic changes in the parent cells are mirrored in the design of the secreted EVs. As a result, EVs have been investigated for a wide range of medicinal and diagnostic uses in different hematological diseases. EVs have only recently been studied in the context of Chronic Myeloid Leukemia (CML), a blood malignancy defined by the chromosomal rearrangement t(9;22) and the fusion gene BCR-ABL1. The findings range from the impact on pathogenesis to the possible use of EVs as medicinal chemical carriers. This review aims to provide for the first time an update on our understanding of EVs as carriers of CML biomarkers for minimal residual disease monitoring, therapy response, and its management, as well as the limited reports on the use of EVs as therapeutic shuttles for innovative treatment approaches.

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Exosome: From leukemia progression to a novel therapeutic approach in leukemia treatment

Cited by 11 publications

References 187 publications

Enhancing the anti-leukemia immunity of leukemia-derived exosome-based vaccine by downregulation of PD-L1 expression

Enhancing the anti-leukemia immunity of leukemia-derived exosome-based vaccine by downregulation of PD-L1 expression

Paediatric pre‐B acute lymphoblastic leukaemia‐derived exosomes regulate immune function in human T cells

Extracellular vesicles in the Chronic Myeloid Leukemia scenario: an update about the shuttling of disease markers and therapeutic molecules

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