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MicroRNA analysis of Natural Killer cell-derived exosomes: the microRNA let-7b-5p is enriched in exosomes and participates in their anti-tumor effects against pancreatic cancer cells.
Di Pace, Anna Laura; Pelosi, Andrea; Fiore, Piera Filomena; Tumino, Nicola; Besi, Francesca; Quatrini, Linda; Santopolo, Silvia; Vacca, Paola; Moretta, Lorenzo.
Afiliación
  • Di Pace AL; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Pelosi A; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Fiore PF; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Tumino N; Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Besi F; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Quatrini L; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Santopolo S; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Vacca P; Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, Rome, Italy.
  • Moretta L; Tumor Immunology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
Oncoimmunology ; 12(1): 2221081, 2023.
Article en En | MEDLINE | ID: mdl-37304055
Natural Killer (NK) cells are important components of the immune system in the defense against tumor growth and metastasis. They release exosomes containing proteins and nucleic acids, including microRNAs (miRNAs). NK-derived exosomes play a role in the anti-tumor NK cell function since they are able to recognize and kill cancer cells. However, the involvement of exosomal miRNAs in the function of NK exosomes is poorly understood. In this study, we explored the miRNA content of NK exosomes by microarray as compared to their cellular counterparts. The expression of selected miRNAs and lytic potential of NK exosomes against childhood B acute lymphoblastic leukemia cells after co-cultures with pancreatic cancer cells were also evaluated. We identified a small subset of miRNAs, including miR-16-5p, miR-342-3p, miR-24-3p, miR-92a-3p and let-7b-5p that is highly expressed in NK exosomes. Moreover, we provide evidence that NK exosomes efficiently increase let-7b-5p expression in pancreatic cancer cells and induce inhibition of cell proliferation by targeting the cell cycle regulator CDK6. Let-7b-5p transfer by NK exosomes could represent a novel mechanism by which NK cells counteract tumor growth. However, both cytolytic activity and miRNA content of NK exosomes were reduced upon co-culture with pancreatic cancer cells. Alteration in the miRNA cargo of NK exosomes, together with their reduced cytotoxic activity, could represent another strategy exerted by cancer to evade the immune response. Our study provides new information on the molecular mechanisms used by NK exosomes to exert anti-tumor-activity and offers new clues to integrate cancer treatments with NK exosomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / MicroARNs / Exosomas Límite: Child / Humans Idioma: En Revista: Oncoimmunology Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / MicroARNs / Exosomas Límite: Child / Humans Idioma: En Revista: Oncoimmunology Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos