Cancer-derived extracellular vesicles in natural killer cell immune evasion: Molecular mechanisms and therapeutic insights

Natural killer cells are innate lymphocytes equipped with the ability to rapidly identify and eliminate cancer cells. However, cancer cells release nanosized extracellular vesicles that can induce an immunosuppressive tumor microenvironment, subsequently hindering natural killer cell immunosurveillance. Studies have reported that extracellular vesicles derived from different cancers, such as acute myeloid leukemia, melanoma, mesothelioma, head and neck squamous carcinoma, lung carcinoma, breast cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, can induce natural killer cell dysfunction by suppressing cytolytic proteins and downregulating expression of receptors involved in the recognition of oncogenic cells. Additionally, cancer-derived extracellular vesicles can interfere with natural killer cell survival, proliferation, cell migration, and metabolic functions. Therefore, extracellular vesicle-induced natural killer cell suppression has emerged as a key target for research and new therapeutic approaches to recover and enhance the tumoricidal potential of these immune cells. Here, we summarize the current knowledge regarding cancer-derived extracellular vesicles and natural killer cell interactions, their role in immunosuppression, implications for developing efficient cellular immunotherapies and outstanding questions in this field.