Tumor-derived exosomes (TDEs) play an important role in multiple aspects of cancer biology, and there are many studies that clearly show that TDES can also promote tumor growth by negatively affecting anti-tumor immunity. Natural killer cells (NK) act as important sentinel cells in the immune monitoring system, and can identify malignant cells in advance and inhibit tumor development and metastasis without the need for additional activation.
Based on this theory, in vitro expansion of NK cells/NK cell lines, such as NK 92 cells, is widely concerned and studied as a promising means of cancer immunotherapy. However, using a variety of strategies, including secreting exosomes, cancer cells are able to disrupt the NK cell response. This article reviews the role of TDEs in cancer-induced NK cell damage from a mechanical point of view.
Recently, researchers at the Medical School of Isfahan Medical University published a review article in the journal Molecular Cancer titled "Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy". The role of TDEs in tumor-induced NK cell damage and its mechanisms were reviewed, and the clinical significance and potential pathways of the effect of TDEs on NK cells in tumor immunotherapy were also discussed.
Uptake/interaction of TDEs with NK cells
Tumor-derived exosomes (TDEs) can be absorbed by various cells through plasma membrane fusion, endocytosis, phagocytosis, microcytosis, and lipid raft-mediated internalization, preferentially by immune cells. Uptake/interaction of tumor exosomes with immune cells is thought to be involved in immunosuppression and tumor escape. Multiple studies have shown that tumor exosomes can carry them to NK cells through fusion with cell membranes, thereby hindering the anti-tumor function of NK cells.
Immune synapses between tumor-derived exosomes and NK cells
Tumor cells release large amounts of immunosuppressive exosomes into the tumor microenvironment and circulation, interacting with NK cells and delivering their inhibitory contents to NK cells. A large number of biomolecules, including ligands of NK cells' activated receptor NKG2D (MICA/B), programmed death ligands (PD-L1) and human transformation growth factor-β1 (TGF-b) appear on exosomes that bind to homologous receptors on NK cells, inducing downstream signaling and inhibiting their antitumor activity.
In summary, an in-depth understanding of the pathological roles and mechanisms of TDE-mediated NK cell dysfunction will allow us to further enhance the therapeutic potential of NK cells.
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