Roles and application of exosomes in the development, diagnosis and treatment of gastric cancer

Table 1 Exosome-mediated regulation of immunity

Origin of exosomes	Target cells	Functional molecules	Mechanisms	Ref.
DC	CD4 and CD8+ T cells	CD80 and IL-2	Induce anti-tumor immune response	[18]
Treg	T cells and B cells	IL-35	Induce peripheral tolerance of T cells and B cells by transferring IL-35	[21]
Treg	Th-1	Let-7d	Inhibition of Th1 cell proliferation and cytokine release	[22]
TAM	CD4+ T cells	miR-29a-3p miR-21-5p	Induce Treg/Th17 imbalance	[25]
NK	T cells	miR-186	Inhibition of tumorigenic potential and TGFβ-dependent immune escape	[31]
TDE	CD4 and CD8+ T cells	IL-2	Inhibition of IL-2-mediated proliferation of CD4 and CD8 T cells	[34]
TDE	T cells	FasL and CD3-ζ	Induce T cell apoptosis or inhibit T cell receptor signaling	[35]
GC-exosomes	T cells	PI3K proteasome and caspases 3, 8, 9	Mediate degradation of PI3K proteasome and activation of caspases 3, 8 and 9, and induce apoptosis of Jurkat T cells	[36]
GC-exosomes	CD8+ T cells	IL-10	Inducing PD1 signal can effectively enhance the immunosuppressive activity	[37]
GC-exosomes	MSCs	NF-κB signaling pathway	Promote macrophage phagocytosis, up-regulate the secretion of proinflammatory factors and promote the activation of CD69 and CD25	[38]
TDE	DC	miR-212-3p	Inhibit MHC II transcription factor RFXAP in dendritic cells	[39]

DC: Dendritic cell; IL: Interleukin; Treg: Regulatory T cell; Th1: Type 1 T helper; TAM: Tumor-associated macrophage; NK: Natural killer; TGF: Transforming growth factor; TDE: Tumor-derived exosome; GC: Gastric cancer; PD1: Programmed cell death 1; MSC: Mesenchymal stem cell; NF-κB: Nuclear factor kappa-beta; MHC: Major histocompatibility complex; FasL: Fas ligand.

Table 2 Role of exosomes cargo in initiation and progression of gastric cancer

Type	Contents	Mechanisms	Function	Ref.
Protein	YB-1	Up-regulation of angiogenic factors in endothelial cells	Promote gastric cancer angiogenesis	[45]
miRNA	miR-519a-3p	Causes M2-like polarization of macrophages	Induce angiogenesis and promote pre-metastatic niche formation	[46]
Protein	X26nt	Decrease vascular endothelial cadherin	Promote angiogenesis	[47]
circRNA	circ29	Regulates the VEGF pathway in endothelial cells	Promote angiogenesis	[48]
Protein	GKN1	Tumor suppressor protein	Inhibit cell proliferation and induce cell apoptosis	[51]
Protein	TRIM3	TRIM3 knockdown regulates stem cell factors and EMT regulators	Promote the growth and metastasis of gastric cancer	[52]
Protein	GC-exosome	Activation of NF-κB activates macrophages in human peripheral blood mononuclear cells	Promote tumor cell proliferation and migration	[53]
Protein	GC-exosome	Induce pericytes to transform into CAFs	Induce malignant progression of cancer	[58]
Protein	CD97	Activate the MAPK signaling pathway	Promote cell proliferation and invasion	[54]

MiRNA: MicroRNA; circRNA: Circular RNA; VEGF: Vascular endothelial growth factor; GC: Gastric cancer; NF-κB: Nuclear factor kappa-beta; EMT: Epithelial-to-mesenchymal transition; CAFs: Cancer-associated fibroblast.

Table 3 Application of exosomes as biomarkers in gastric cancer

TDE-molecule	TDEs source	Application	Ref.
miR10b-5p	Serum	Diagnosis and prognosis	[74]
miR296-5p
LINC00152	Plasma	Diagnosis	[76]
TRIM3	Serum	Diagnosis	[52]
lncUEGC1	Serum	Early diagnosis of gastric cancer	[77]
lncUEGC2
TGF-β1	Serum	Pathological stage and lymph node metastasis	[66]
miR-21	Malignant ascites, peritoneal lavage fluid and culture supernatants	Serosal invasion	[78]
miR-1225-5p

TDE: Tumor-derived exosome.