The Roles of Tumor-Derived Exosomes in Cancer Pathogenesis

Table 1

Representative studies on the immunogenicity of tumor-derived exosomes and tumor exosome-based cancer vaccines.

Parental tumor type/exosome source	Exosome application/modification	Model	Results	References
Mouse mammary adenocarcinoma, melanoma, mesothelioma, mastocytoma, human melanoma	BMDC pulsed with exo were injected into mice with established tumor	Mouse	Exo transfer tumor antigen to DC, induce CD8+ T cell-dependent antitumor effects on both syngeneic and allogeneic mouse tumors	[33]
Malignant effusions of melanoma patients	MDDCs-pulsed exo were used to stimulate lymphocytes	Human; ex vivo	DCs pulsed with exo cross-present mart-1 antigen to and expand antigen-specific CTLs	[32]
Human malignant glioma	Human DCs were incubated with exo	Human; ex vivo	DCs incubated with exo activate glioma-specific CTL which kills autologous glioma cells; in vitro	[36]
Human CEA+ colon, lung; carcinoma	Exo were isolated from heat-stressed tumor cells	Mouse, Human; ex vivo	Exo immunization efficiently prime antigen-specific CTL with antitumor effects in mice; exo-pulsed autologous DCs from CEA+ cancer patients induce antigen-specific CTL response	[34]
Mouse B lymphoma	Parental cells were heat-shocked	Mouse	Exo induce DC maturation and stimulate both protective and therapeutic antitumor immune responses	[40]
Mouse colon carcinoma and melanoma	Parental cells were heat-treated	Mouse	Exo contain elevated levels of Hsp70, elicit Th1 response and therapeutically regress established autologous and allogeneic tumors	[41]
Mouse melanoma	Parental cells were engineered to express membrane-bound Hsp 70	Mouse	Exo stimulate Th1 and CTL response more efficiently than exo derived from heat-shocked cells expressing cytoplasmic Hsp70	[42]
Mouse lung carcinoma	Parental cells were heat-stressed	Mouse	Exo contain enriched chemokines, attract/activate DCs and T cells more potently and induce antitumor response	[43]
Human CEA+ tumor cells	Parental cells were transfected with AdhIL-18	Human ex vivo	Exo/IL-18 chemoattract DCs and T cells and enhance Th1 cytokine release. Exo/IL18-pulsed DCs induced potent CTL response	[37]
Mouse OVA+ thymoma	Parental cells were transfected with AdmIL-12	Mouse	Vaccination of exo/IL-2 induces antigen-specific Th1 and CTL responses and inhibits tumor growth	[39]
Human renal cancer	Parental cells were modified to express GPI-IL-12	In vitro	Exo/IL-12 promote IFN-γ release and the induction of antigen-specific CTLs	[38]
Mouse lymphoma	Exo were surfaced anchored with the superantigen SEA by protein transfer	Mouse	Immunization with exo/SEA-TM efficiently inhibits tumor growth and induces tumor-specific CTLs	[44]
Mouse fibrosarcoma	OVA antigen was targeted to exo membrane by transfecting parental cells with OVA coupled to lactadherin C1C2 domain	Mouse	Tumors secreting exo-bound OVA elicit a stronger anti-OVA response and grow slowly in vivo	[45]
Human ovarian cancer ascites	Exo were purified from malignant ascites and quality assessed	Preceding of a clinical trial	A method for the preparation of GMP-grade exosomes used in combination of mature DCs for a clinical trial is described	[46]
Ascites from colorectal cancer; patients	Exo were purified and used to immunize patients either alone or with GM-CSF	Phase I clinical trial	Exo therapy is well-tolerated; exo plus GM-CSF induce beneficial tumor-specific CTL responses in patients with colorectal cancer	[47]

Abbreviations: Exo, exosomes; MDDCs: monocyte-derived DCs; Ad: adenovirus; GM-CSF: granulocyte-macrophage colony-stimulating factor.