Fig. 2

NK cells can secrete exosomes with various cargo. These exosomes contain TSG101, Alix, CD9, CD63, CD81, and CD82. In addition to typical exosome markers, NK cell-derived exosomes exhibit specific biomarkers such as CD56, DNAM-1, NKp30, NKp44, NKp46, and NKG2D. NK cell-derived exosomes contain perforin and express FasL, which contribute to the cytotoxicity effects of these vesicles. Cytotoxic proteins such as perforin, granzyme A, granzyme B, and granulysin can induce apoptosis in target cells. Since the mechanism of action of NK cells and their exosomes against tumor and virus-infected cells is relatively similar, it seems that NK cell exosomes use the following mechanisms to fight against virus-infected cells. NK cell derived-exosomes can overexpress the NK activating receptors NKp30, NKp44, NKp46, and NKG2D and be able to educate naïve NK cells, which evolve into a memory-like state, with increased cytotoxicity and enhanced tumor-killing capacity. NK cell-derived exosomes were rich in miR-10b-5p, miR-155-5p, or miR-92a-3p. T cell response can be the putative target of these small RNAs. So, NK cell-derived exosomes promote Th1 differentiation and increase IL-2 and IFN-γ production. On the other hand, the polarization of monocyte to monocyte-derived dendritic cells can be affected by NK cell-derived exosomes, and these vesicles increased the expression of MHC-II and CD86 on these cells. NK cell-derived exosomes can shift macrophage polarization to M1. As mentioned, the existence of FasL and TRAIL on the surface of NK cell-derived exosomes and cargo of perforin, granzyme A, granzyme B, and granulysin were confirmed by multiple studies supporting direct cytotoxic effects of NK cell exosomes in the face of target cells. miRNAs are another tools that these valuable exosomes use to inhibit target cells