Extracellular vesicles originating from melanoma cells promote dysregulation in haematopoiesis as a component of cancer immunoediting.

Autor: Mamand DR; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden, Karolinska Institute, Stockholm, Sweden., Bazaz S; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden., Mohammad DK; Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.; College of Agricultural Engineering Sciences, Salahaddin University-Erbil, Erbil, Iraq., Liang X; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Karolinska ATMP Center, ANA Futura, Huddinge, Sweden, Karolinska Institute, Stockholm, Sweden., Pavlova S; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Karolinska ATMP Center, ANA Futura, Huddinge, Sweden, Karolinska Institute, Stockholm, Sweden., Mim C; Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden., Gabrielsson S; Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden., Nordin JZ; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Clinical Immunology and Transfusion Medicine (KITM), Karolinska University Hospital, Stockholm, Sweden.; Karolinska ATMP Center, ANA Futura, Huddinge, Sweden, Karolinska Institute, Stockholm, Sweden., Wiklander OPB; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden, Karolinska Institute, Stockholm, Sweden.; Karolinska ATMP Center, ANA Futura, Huddinge, Sweden, Karolinska Institute, Stockholm, Sweden., Abedi-Valugerdi M; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden., El-Andaloussi S; Biomolecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Karolinska ATMP Center, ANA Futura, Huddinge, Sweden, Karolinska Institute, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Journal of extracellular vesicles [J Extracell Vesicles] 2024 Jul; Vol. 13 (7), pp. e12471.
DOI: 10.1002/jev2.12471
Abstrakt: Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour development. Here, the role of in vitro generated B16F10 tumour cell-derived extracellular vesicles (tEVs) as indirect cellular communicators, participating in tumour-induced dysregulation of haematopoiesis, was explored. The isolated tEVs displayed features of small EVs with a size range of 100-200 nm, expressed the common EV markers CD63, CD9, and Alix, and had a spherical shape with a lipid bilayer membrane. Proteomic profiling revealed significant levels of angiogenic factors, particularly vascular endothelial growth factor (VEGF), osteopontin, and tissue factor, associated with the tEVs. Systemic administration of these tEVs in syngeneic mice induced splenomegaly and disrupted haematopoiesis, leading to extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and the development of anaemia. These effects closely mirrored those observed in tumour-bearing mice and were not seen after heat inactivating the tEVs. In vitro studies demonstrated that tEVs independently induced the expansion of bone marrow granulocytic myeloid suppressor cells and B cells while reducing the frequency of cells in the erythropoietic lineage. These effects of tEVs were significantly abrogated by the blockade of VEGF or heat inactivation. Our findings underscore the important role of tEVs in dysregulating haematopoiesis during the immune escape phase of cancer immunoediting, suggesting their potential as targets for addressing immune evasion and reinstating normal hematopoietic processes.
(© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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