Table 1.

Characteristics of the immunomodulating proteins from tumor-derived exosomes presented in this review. PD-L1: programmed death-ligand 1; HNSCC: head and neck squamous cell carcinoma; IL: interleukin; IFN: interferon; TNF: tumor necrosis factor; EMT: epithelio-mesenchymal transition; MDSC: myeloid derived suppressor cells, NSCLC: non-small cell lung cancer; CRC: colorectal cancer; NPC: nasopharyngeal carcinoma.

Exosomal Protein	Type of Cancer	Source of Exosomes	Target Protein	Potential Exosome-Related Functions in Cancer
PD-L1	HNSCC	Plasma [58,59,60]	PD-1	Decreases the secretion of IL-2 and IFN-γ Suppresses the proliferation of CD4+ T-cells Induces apoptosis in CD8+ T-cells Enhances the suppressor activity of T-reg cells
	Glioblastoma	Plasma; Primary cancer cells lines G34, G35, G44, G157 [61]		Inhibits CD4+ and CD8+ T-cell activation
	Breast	Cancer cell lines MDA-MB-231, HCC1954, SKBR3, EFM-192A [62,63,64]		Decreases the secretion of IL-2 Suppresses T-cell activation
	Prostate	Cancer cell lines DU145, PC3, LnCap, TRAMP-C2 [65]		Inhibits T-cell activation Causes T-cell exhaustion Reduces spleen size
	Melanoma	Plasma; Cancer cell lines SK-Mel-2, SK-Mel-28, Mel624 and WM9 (human) and B16F10 (murine) [54,56,65]		Reduces production of granzyme B, IFN-γ, IL-2, and TNF-α Inhibits proliferation of T-cells Reduces migration of CD4+ and CD8+ T-cells
	NSCLC	Serum; plasma; Cancer cell lines A549, H460, H1975 [66,67]		Decreases IFN-γ production in a dose-dependent manner
	Lung Squamous Cell Carcinoma and adenocarcinoma	Plasma [68]		Inhibits INF-γ production Promotes apoptosis of CD8+ T-cells Promotes tumor growth
	Gastric cancer	Plasma [69,70]		Reduces CD4+ and CD8+ T-cell numbers, and reduces granzyme B production Suppresses T-cell activation
	Oral-oesophageal	HNSCC cancer cell lines SCC90 (human) and SCCVII (murine) [71].		Reduces migration of CD4+ and CD8+ T-cells
TIM-3	Osteosarcoma	Cancer cell line MG63 [55]	(Non Available)	Promotes the pro-tumoral M2 phenotype in macrophages Increases invasion, migration, EMT of osteosarcoma cells; increases lung metastasis in in vivo nude mouse model
	NSCLC	Plasma [72]		Associates to malignancy and promotes metastasis
Gal-9	NPC	Plasma (patients) [73] Plasma from C15 and C17 xenografted mice [73]	TIM-3	Induces apoptosis in helper T-cells
		NPC xenografts cell lines (C15 and C17) supernatant [74]		Suggested to inhibit proliferation of peripheral blood resting T-cells
		Cancer cell lines TW03 [75]	(Non Available)	Promotes maturation into MDSCs from myeloid CD33+ cells
CD73/CD39	Bladder, breast, colorectal	Cancer cell lines HT1376 (bladder), CACO2 (CRC), MCF7 (breast) [76]	Adenosine Receptors	Produces adenosine (immunosuppressor)
	Prostate	Cancer cell lines DU145, PC3 [76,77]		Produces adenosine (immunosuppressor)
	Mesothelioma	Pleural effusion; custom cancer cell line (Meso) [76]		Reduces proliferation and activity (IL-2, TNF-α secretion) of activated T-cells
	HNSCC	Plasma; cancer cell line UMSCC47 [78]		Promotes A2BR-mediated polarization of macrophages toward a pro-tumoral M2-like phenotype, leading to increased angiogenesis
		Plasma [79]		Produces adenosine (immunosuppressor) Induces adenosine production by CD39+ T-regs
		Plasma [59]		Produces adenosine (immunosuppressor) especially at later cancer stages