Table 2.

Summary of tumor EV-mediated reprogramming of immune microenvironment in PMN

Immune cell being targeted	PMN site	EV cargo	Reprogramming mechanism	Source tumor
Macrophages	Lung, brain	Annexin II	Activate proinflammatory signaling	Breast cancer
	Lung	Not defined	Secrete immunosuppressive factor release, decrease phagocytosis and efferocytosis	osteosarcoma cells
	Lymph node		Alter glycolytic metabolism, upregulate PD-L1 expression	Lung cancer
Kupffer cells	Liver	MIF	TGFβ secretion	PDAC
Hematopoietic progenitors	Lung, liver	VEGF	Mobilization and recruitment of hematopoietic progenitors to distant sites	Lung cancer, melanoma
Bone marrow derived cells	Lung, bone	MET	Pro-vasculogenic phenotype differentiation	Melanoma
	Not defined	MUC1, palmitoylated proteins	MDSC differentiation	AML
	Lymph node	miR-21	Monocytic MDSC differentiation	Esophageal squamous cell carcinoma, lung cancer, glioma
	Not defined	miR-10, miR-29a, miR-92a	MDSC differentiation	Glioma
		miR-107		Gastric cancer
		miR-155		Chronic lymphocytic leukemia
	Lung	miR-9, miR-181a		Breast cancer
	Not defined	miR-1246		GBM
		HSP86		Melanoma
		HSP70		Breast cancer, lung cancer, ovarian cancer
	Lung	HSP72		CRC, Lung cancer
	Not defined	Not defined	Induce immuno-evasive phenotype differentiation, block DC differentiation, maturation and migration	Lung cancer, breast cancer
Neutrophils			NET formation	Breast cancer
			NET formation, promote life span	Melanoma
		HMGB1	Promote life span and N2 polarization	Gastric cancer
		RNAs (long interspersed nuclear elements, short interspersed nuclear elements, and long terminal repeats)	Sustain survival and polarization towards a pro-tumorigenic phenotype	CRC
NK		Not defined	Reduce NK recruitment and migration by CXCR3 downregulation	AML
		TGFβ1	Impair NK proliferation by downregulation of IL-2R	Mesothelioma, prostate cancer
			NK dysfunction by downregulation of NKG2D	PDAC, AML, mesothelioma, prostate cancer, renal cell carcinoma
			NK dysfunction by downregulation of NKG2D and upregulation of NKG2A	Oral cancer
Treg			Skew expansion or induce phenotypic alteration of T cells towards Tregs	CRC
NK	Lung	Not defined	Block IL-2-mediated NK proliferation	Breast cancer
	Not defined	NKG2DLs (MICA/B)	NK tolerance by downregulation of NKG2D	Liver cancer, CRC, melanoma, mesothelioma, prostate cancer
	Liver	lncRNA-SNHG10	Impaire NK proliferation and toxicity by activation of TGFβ signaling	CRC
CD8+ T	Not defined	FasL, APO2L/TRAIL	Suppress CD8+ T cell proliferation and promote apoptosis	Melanoma, PDAC, Ovarian cancer
	Liver	FasL, TRAIL		CRC
	Lymph node	FasL		Oral cancer, head and neck cancer
	Not defined	PD-L1	Suppress T cell proliferation, mobility, cytotoxicity and cytokine release	Melanoma, lung cancer, gastric cancer, prostate cancer, CRC, GBM, head and neck cancer, breast cancer
CD4+ T, CD8+ T, NK		FasL, TRAIL, CTLA4	Suppresse CD8+ T cell proliferation and cytokine release and CD4+ T /NK cell activation and promote macrophage differentiation into M2 phenotype	GBM
CD4+ T, CD8+ T	Lymph node	TIM3, galectin-9	Promote T cell exhaustion	Lung cancer
	Not defined	ARGI	T cell dysfunction by L-arginine depletion	Ovarian cancer
T cell, NK		CD39, CD73	T/NK cell dysfunction and inhibit clonoal expansion through adenosine production	Bladder cancer, CRC, prostate cancer, breast cancer, mesothelioma, GBM
T cell		TnC	Inhibit T cell proliferation	GBM
γδT cell	Lymph node	SNHG16	Induce a CD73+ Treg phenotype	Breast cancer
B cell		Not defined	Promote plasma cell amplification and tumor-promoting autoantibody production	Melanoma