Research progress of inducing effect of tumor-derived exosomes on dendritic cells and cytokine-induced killer cells_West China Medical Journal

Authors：

LIU Siwen ,  DONG Lihua

West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

DONG Lihua, Email: donglihua11@163.com

Keywords：

Exosome; Dendritic cell; Cytokine-induced killer cell; Adoptive immunity

DOI：

10.7507/1002-0179.201705122

Video：

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Abstract Full text Figures/Tables Video References Cited by

Tumor-derived exosomes play a role in helping tumor cells with escape from immune surveillance, and it may also activate tumor-specific immune responses to eradicate tumor cells. Tumor cells release exosomes with major histocompatibility complex molecules and antigenic peptides on the surface membranes, which can induce dendritic cells (DC) and cytokine-induced killer (CIK) cells in vitro to produce the tumor antigen-specific T cells, and the obtained DC-CIK cells have a dual antitumor function with specificity and non specificity. This provides a new method for the treatment of cancers. This review briefly summarized the latest progress of adoptive immunotherapy with exosomes and DC-CIK.

Citation： LIU Siwen, DONG Lihua. Research progress of inducing effect of tumor-derived exosomes on dendritic cells and cytokine-induced killer cells. West China Medical Journal, 2018, 33(4): 435-441. doi: 10.7507/1002-0179.201705122 Copy

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2.	Ishikura S. Optimal radiotherapy for non-small-cell lung cancer: current progress and future challenges. Gen Thorac Cardiovasc Surg, 2012, 60(3): 127-131.
3.	Bretthauer M. Evidence for colorectal cancer screening. Best Pract Res Clin Gastroenterol, 2010, 24(4): 417-425.
4.	Ma Y, Zhang Z, Tang L, et al. Cytokine-induced killer cells in the treatment of patients with solid carcinomas: a systematic review and pooled analysis. Cytotherapy, 2012, 14(4): 483-493.
5.	Trams EG, Lauter CJ, Salem N, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta, 1981, 645(1): 63-70.
6.	Vlassov AV, Magdaleno S, Setterquist R, et al. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta, 2012, 1820(7): 940-948.
7.	Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr Opin Cell Biol, 2009, 21(4): 575-581.
8.	Théry C, Boussac M, Véron P, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol, 2001, 166(12): 7309-7318.
9.	Ekström EJ, Bergenfelz C, von Bülow V, et al. WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells. Mol Cancer, 2014, 13: 88.
10.	Zhang X, Yuan X, Shi H, et al. Exosomes in cancer: small particle, big player. J Hematol Oncol, 2015, 8: 83.
11.	Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002, 2(8): 569-579.
12.	Zöller M. Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer, 2009, 9(1): 40-55.
13.	Wubbolts R, Leckie RS, Veenhuizen PT, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem, 2003, 278(13): 10963-10972.
14.	Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol, 2008, 110(1): 13-21.
15.	Silva J, García V, Zaballos Á, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J, 2011, 37(3): 617-623.
16.	Thind A, Wilson C. Exosomal miRNAs as cancer biomarkers and therapeutic targets. J Extracell Vesicles, 2016, 5: 31292.
17.	Tauro BJ, Greening DW, Mathias RA, et al. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics, 2013, 12(3): 587-598.
18.	Peinado H, Alečković M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through Met. Nat Med, 2012, 18(6): 883-891.
19.	Hood JL, San RS, Wickline SA. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res, 2011, 71(11): 3792-3801.
20.	Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol, 2008, 10(5): 619-624.
21.	Skog J, Würdinger T, Van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol, 2008, 10(12): 1470-1476.
22.	Thakur BK, Zhang H, Becker A, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res, 2014, 24(6): 766-769.
23.	Schott M, Seissler J. Dendritic cell vaccination: new hope for the treatment of metastasized endocrine malignancies. Trends Endocrinol Metab, 2003, 14(4): 156-162.
24.	Roche PA, Furuta K. The ins and outs of MHC class Ⅱ-mediated antigen processing and presentation. Nat Rev Immunol, 2015, 15(4): 203-216.
25.	Zehner M, Marschall AL, Bos E, et al. The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells. Immunity, 2015, 42(5): 850-863.
26.	Schrama D, Thor Straten P, Fischer WH, et al. Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity, 2001, 14(2): 111-121.
27.	Thompson ED, Enriquez HL, Fu YX, et al. Tumor masses support naive T cell infiltration, activation, and differentiation into effectors. J Exp Med, 2010, 207(8): 1791-1804.
28.	Sallusto F, Cella M, Danieli C, et al. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class Ⅱ compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995, 182(2): 389-400.
29.	Jiang W, Swiggard WJ, Heufler C, et al. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature, 1995, 375(6527): 151-155.
30.	Montecalvo A, Larregina AT, Shufesky WJ, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood, 2012, 119(3): 756-766.
31.	Andre F, Schartz NE, Movassagh M, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet, 2002, 360(9329): 295-305.
32.	Sangiolo D. Cytokine induced killer cells as promising immunotherapy for solid tumors. J Cancer, 2011, 2(1): 363-368.
33.	Wang XP, Xu M, Gao HF, et al. Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma. World J Gastroenterol, 2013, 19(19): 2956-2962.
34.	Schmidt TL, Negrin RS, Contag CH. A killer choice for cancer immunotherapy. Immunol Res, 2014, 58(2/3): 300-306.
35.	Hanahan D, Weinberg RA. The hallmarks of cancer. Cell, 2000, 100(1): 57-70.
36.	Hazelrigg MR, Hirsch JI, Merchant RE. Distribution of adoptively transferred, tumor-sensitized lymphocytes in the glioma-bearing rat. J Neurooncol, 2002, 60(2): 143-150.
37.	Skitzki J, Craig RA, Okuyama R, et al. Donor cell cycling, trafficking, and accumulation during adoptive immunotherapy for murine lung metastases. Cancer Res, 2004, 64(6): 2183-2191.
38.	Liu H, Li J, Wang F, et al. Comparative study of different procedures for the separation of peripheral blood mononuclear cells in cytokine-induced killer cell immunotherapy for hepatocarcinoma. Tumour Biol, 2015, 36(4): 2299-2307.
39.	Li H, Wang C, Yu J, et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery. Cytotherapy, 2009, 11(8): 1076-1083.
40.	Alters SE, Gadea JR, Sorich M, et al. Dendritic cells pulsed with CEA peptide induce CEA-specific CTL with restricted TCR repertoire. J Immunother, 1998, 21(1): 17-26.
41.	Märten A, Ziske C, Schöttker B, et al. Interactions between dendritic cells and cytokine-induced killer cells Lead to an activation of both populations. J Immunother, 2001, 24(6): 502-510.
42.	Zhong R, Teng J, Han B, et al. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother, 2011, 60(10): 1497-1502.
43.	Cui Y, Yang X, Zhu W, et al. Immune response, clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients. Oncol Lett, 2013, 6(2): 537-541.
44.	Xie S, Wu X, Zhang G, et al. Remarkable regression of a lung recurrence from an undifferentiated embryonal sarcoma of the liver treated with a DC vaccine combined with immune cells: a case report. Cell Immunol, 2014, 290(2): 185-189.
45.	Jung NC, Lee JH, Choi HJ, et al. Dendritic cell immunotherapy combined with cytokine-induced killer cells effectively suppresses established hepatocellular carcinomas in mice. Immunol Invest, 2016, 45(6): 553-565.
46.	Chen H, Xiang Y, Ding P, et al. Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin. J Zhejiang Univ Sci B, 2016, 17(7): 537-544.
47.	Xiang X, Poliakov A, Liu C, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer. 2009, 124(11): 2621-2633.
48.	Yu S, Liu C, Su K, et al. Tumor exosomes inhibit differentiation of bone marrow dendritic cells. J Immunol, 2007, 178(11): 6867-6875.
49.	Wolfers J, Lozier A, Raposo G, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med, 2001, 7(3): 297-303.

1. Videtic GM. Locally advanced non-small cell lung cancer: what is the optimal concurrent chemoradiation regimen?. Cleve Clin J Med, 2012(Electronic Suppl 1): S32-S37.
2. Ishikura S. Optimal radiotherapy for non-small-cell lung cancer: current progress and future challenges. Gen Thorac Cardiovasc Surg, 2012, 60(3): 127-131.
3. Bretthauer M. Evidence for colorectal cancer screening. Best Pract Res Clin Gastroenterol, 2010, 24(4): 417-425.
4. Ma Y, Zhang Z, Tang L, et al. Cytokine-induced killer cells in the treatment of patients with solid carcinomas: a systematic review and pooled analysis. Cytotherapy, 2012, 14(4): 483-493.
5. Trams EG, Lauter CJ, Salem N, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta, 1981, 645(1): 63-70.
6. Vlassov AV, Magdaleno S, Setterquist R, et al. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta, 2012, 1820(7): 940-948.
7. Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr Opin Cell Biol, 2009, 21(4): 575-581.
8. Théry C, Boussac M, Véron P, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol, 2001, 166(12): 7309-7318.
9. Ekström EJ, Bergenfelz C, von Bülow V, et al. WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells. Mol Cancer, 2014, 13: 88.
10. Zhang X, Yuan X, Shi H, et al. Exosomes in cancer: small particle, big player. J Hematol Oncol, 2015, 8: 83.
11. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002, 2(8): 569-579.
12. Zöller M. Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer, 2009, 9(1): 40-55.
13. Wubbolts R, Leckie RS, Veenhuizen PT, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem, 2003, 278(13): 10963-10972.
14. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol, 2008, 110(1): 13-21.
15. Silva J, García V, Zaballos Á, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J, 2011, 37(3): 617-623.
16. Thind A, Wilson C. Exosomal miRNAs as cancer biomarkers and therapeutic targets. J Extracell Vesicles, 2016, 5: 31292.
17. Tauro BJ, Greening DW, Mathias RA, et al. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics, 2013, 12(3): 587-598.
18. Peinado H, Alečković M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through Met. Nat Med, 2012, 18(6): 883-891.
19. Hood JL, San RS, Wickline SA. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res, 2011, 71(11): 3792-3801.
20. Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol, 2008, 10(5): 619-624.
21. Skog J, Würdinger T, Van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol, 2008, 10(12): 1470-1476.
22. Thakur BK, Zhang H, Becker A, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res, 2014, 24(6): 766-769.
23. Schott M, Seissler J. Dendritic cell vaccination: new hope for the treatment of metastasized endocrine malignancies. Trends Endocrinol Metab, 2003, 14(4): 156-162.
24. Roche PA, Furuta K. The ins and outs of MHC class Ⅱ-mediated antigen processing and presentation. Nat Rev Immunol, 2015, 15(4): 203-216.
25. Zehner M, Marschall AL, Bos E, et al. The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells. Immunity, 2015, 42(5): 850-863.
26. Schrama D, Thor Straten P, Fischer WH, et al. Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity, 2001, 14(2): 111-121.
27. Thompson ED, Enriquez HL, Fu YX, et al. Tumor masses support naive T cell infiltration, activation, and differentiation into effectors. J Exp Med, 2010, 207(8): 1791-1804.
28. Sallusto F, Cella M, Danieli C, et al. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class Ⅱ compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995, 182(2): 389-400.
29. Jiang W, Swiggard WJ, Heufler C, et al. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature, 1995, 375(6527): 151-155.
30. Montecalvo A, Larregina AT, Shufesky WJ, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood, 2012, 119(3): 756-766.
31. Andre F, Schartz NE, Movassagh M, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet, 2002, 360(9329): 295-305.
32. Sangiolo D. Cytokine induced killer cells as promising immunotherapy for solid tumors. J Cancer, 2011, 2(1): 363-368.
33. Wang XP, Xu M, Gao HF, et al. Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma. World J Gastroenterol, 2013, 19(19): 2956-2962.
34. Schmidt TL, Negrin RS, Contag CH. A killer choice for cancer immunotherapy. Immunol Res, 2014, 58(2/3): 300-306.
35. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell, 2000, 100(1): 57-70.
36. Hazelrigg MR, Hirsch JI, Merchant RE. Distribution of adoptively transferred, tumor-sensitized lymphocytes in the glioma-bearing rat. J Neurooncol, 2002, 60(2): 143-150.
37. Skitzki J, Craig RA, Okuyama R, et al. Donor cell cycling, trafficking, and accumulation during adoptive immunotherapy for murine lung metastases. Cancer Res, 2004, 64(6): 2183-2191.
38. Liu H, Li J, Wang F, et al. Comparative study of different procedures for the separation of peripheral blood mononuclear cells in cytokine-induced killer cell immunotherapy for hepatocarcinoma. Tumour Biol, 2015, 36(4): 2299-2307.
39. Li H, Wang C, Yu J, et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery. Cytotherapy, 2009, 11(8): 1076-1083.
40. Alters SE, Gadea JR, Sorich M, et al. Dendritic cells pulsed with CEA peptide induce CEA-specific CTL with restricted TCR repertoire. J Immunother, 1998, 21(1): 17-26.
41. Märten A, Ziske C, Schöttker B, et al. Interactions between dendritic cells and cytokine-induced killer cells Lead to an activation of both populations. J Immunother, 2001, 24(6): 502-510.
42. Zhong R, Teng J, Han B, et al. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother, 2011, 60(10): 1497-1502.
43. Cui Y, Yang X, Zhu W, et al. Immune response, clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients. Oncol Lett, 2013, 6(2): 537-541.
44. Xie S, Wu X, Zhang G, et al. Remarkable regression of a lung recurrence from an undifferentiated embryonal sarcoma of the liver treated with a DC vaccine combined with immune cells: a case report. Cell Immunol, 2014, 290(2): 185-189.
45. Jung NC, Lee JH, Choi HJ, et al. Dendritic cell immunotherapy combined with cytokine-induced killer cells effectively suppresses established hepatocellular carcinomas in mice. Immunol Invest, 2016, 45(6): 553-565.
46. Chen H, Xiang Y, Ding P, et al. Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin. J Zhejiang Univ Sci B, 2016, 17(7): 537-544.
47. Xiang X, Poliakov A, Liu C, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer. 2009, 124(11): 2621-2633.
48. Yu S, Liu C, Su K, et al. Tumor exosomes inhibit differentiation of bone marrow dendritic cells. J Immunol, 2007, 178(11): 6867-6875.
49. Wolfers J, Lozier A, Raposo G, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med, 2001, 7(3): 297-303.

West China Medical Journal

Research progress of inducing effect of tumor-derived exosomes on dendritic cells and cytokine-induced killer cells

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