Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses.

ABSTRACT: Small extracellular vesicle (sEV, or exosome) communication among cells in the tumor microenvironment has been modeled mainly in cell culture, whereas their relevance in cancer pathogenesis and progression in vivo is less characterized. Here we investigated cancer-microenvironment interactions in vivo using mouse models of chronic lymphocytic leukemia (CLL). sEVs isolated directly from CLL tissue were enriched in specific miRNA and immune-checkpoint ligands. Distinct molecular components of tumor-derived sEVs altered CD8+ T-cell transcriptome, proteome, and metabolome, leading to decreased functions and cell exhaustion ex vivo and in vivo. Using antagomiRs and blocking antibodies, we defined specific cargo-mediated alterations on CD8+ T cells. Abrogating sEV biogenesis by Rab27a/b knockout

SUBMITTER: Gargiulo E 

PROVIDER: S-EPMC9816815 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature