Table 1 The bimolecular cargo of TDEs and their inhibitory effects on NK cells

Ligands for NKG2D (MICA/B and ULBP1-6)

 AML

Downregulate NKG2D expression and reduce NK-cell cytotoxicity

[23]

 AML

CD34 + exosomes downregulate NK cells activity through decreasing NKG2D levels

[77]

 Metastatic melanoma

Downregulating NKG2D expression on NK cells

[81]

 Saliva exosomes (pancreatic ductal carcinoma (PADC)

Decreases NK cell activation level and triggers downregulation of surface NKG2D

[60]

 HELA, HepG2 and MelJuso

Particle-associated MICA (MICA*008) downregulates NKG2D expression

[82]

 Mesothelioma cell line, prostate cell lines (PC3 or DU145), and EBV-B lymphoblastoid cells (IB4)

Downregulation of surface MICA expression on NK cells

[78]

 Jurkat and Raji cell lines

Exosomal ligands for MICA/B and ULBP1 and 2 downregulate the expression of MICA/B

[83]

 22Rv1( human prostate carcinoma epithelial cell line)

Exosomal MICA/B and ULBPs downregulate NKG2D expression

[79]

 Epithelial ovarian cancer (EOC)

Induce NKG2D downregulation, but do not affect DNAM-1-PVR/nectin-2 pathway

[84]

TGF-b

 AML

Decreases NKG2D expression through SMAD2/3 pathways in NK-92 cells, but do not affect DAP-10 expression

[23]

 AML

Down-regulation of NKG2D receptors and suppression of NK cells activity through the phosphorylation of SMAD1/5/8

[85]

 ALL

Induction of TGF-b signaling by upregulating MDS1 and EVI1 expression

[36]

 Pancreatic cancer

Delivering TGF-b to NK cells and activating the phosphorylation of Smad2/3 signaling pathway

[34]

 Oral cancer

Decreasing the expression of NKp30 and NKG2D on NK cells

[22]

 Non-small cell lung cancer (NSCLC)

Hypoxic MV had higher TGF-b levels and decreased surface NKG2D expression

[37]

 Clear cell renal cell carcinoma (ccRCC)

Abrogating cytotoxic function of NK cells through the activation of the TGF-b/SMAD signaling pathway

[64]

Adenosine and Glucose Metabolism

 AML

Induces adenosine production in TME by expressing CD39/CD73 pair and impair NK cells function via A2AR

[23]

 Glioblastoma

Carrying CD39 and CD73 and mediate NK cells dysfunction

[63]

 Pancreatic cancer cells (L3.6pl)

Reduces the expression of CD71 (transferrin receptor), CD98 (large neutral amino acid transporter) on NK cells

[34]

Fas-L, Survivin, B7-H3 and PD-L1

 Lymphoma

Exosomal Fas-L and Survivin induces NK cell impairment by reducing the expression of perforin, granzyme B, TNF-α, IFN-γ and NKG2D

[86]

 Glioblastoma cells

B7-H3 carrying exosomes impair NK-mediated tumor lysis

[87]

 Melanoma

PD-L1 + exosomes induce NK cells dysfunction through PD-L1/PD1 axis

[88]

RNAs

 Hepatoma

miR-92b containing exosomes alter CD69 expression on NK cells and impair their activity

[89]

 NSCLC

Downregulating CD107a through miR-23a

[37]

 Hepatocellular carcinoma (HCC)

-Ring finger domain 1 RNA (circUHRF1) containing exosomes decrease proportion and infiltration of NK cell

-Exosomal circUHRF1 enhancing TIM-3 expression via degradation of miR-449c-5p

[90]

Colorectal cancer

lncRNA SNHG10 induces inhibin subunit beta C (INHBC), which is involved in the TGF-β signaling pathway

[91]