Microenvironment of tumor-draining lymph nodes: Opportunities for liposome-based targeted therapy

International Journal of Molecular Sciences

Volumn 15, Issue 11, 2014, Pages 20209-20239

  Chandrasekaran, Siddarth ^a   King, Michael R ^a  

^a School of Operations Research and Industrial Engineering   (United States)

Author keywords

Liposomes; Metastasis; Nanomedicine; Tumor microenvironment; Tumor draining lymph nodes

Indexed keywords

ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; INTERLEUKIN 2; LIPID; LIPOSOME; MACROGOL; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ANTIGEN PRESENTING CELL; B LYMPHOCYTE; CANCER IMMUNOTHERAPY; CANCER PATIENT; CLINICAL TRIAL (TOPIC); HUMAN; IMMUNE DEFICIENCY; IMMUNITY; INFLAMMATION; LEUKOCYTE; LYMPH NODE; MOLECULARLY TARGETED THERAPY; MORTALITY; NATURAL KILLER CELL; REVIEW; T LYMPHOCYTE; TUMOR DRAINING LYMPH NODE; TUMOR MICROENVIRONMENT; WORLD HEALTH ORGANIZATION; ANIMAL; CHEMISTRY; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASMS; PATHOLOGY;

ANIMALS; HUMANS; IMMUNOTHERAPY; LIPOSOMES; LYMPH NODES; NEOPLASMS; TUMOR MICROENVIRONMENT;

EID: 84908565751     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms151120209     Document Type: Review

References (193)

1. Thompson, J.F.; McCarthy, W.H.; Bosch, C.M.; O'Brien, C.J.; Quinn, M.J.; Paramaesvaran, S.; Crotty, K.; McCarthy, S.W.; Uren, R.F.; Howman-Giles, R. Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res. 1995, 5, 255-260.
2. Van Trappen, P.O.; Pepper, M.S. Lymphatic dissemination of tumour cells and the formation of micrometastases. Lancet Oncol. 2002, 3, 44-52.
3. Ariel, I.M. Incidence of metastases to lymph nodes from soft-tissue sarcomas. Semin. Surg. Oncol. 1988, 4, 27-29.
4. Jatoi, I.; Hilsenbeck, S.G.; Clark, G.M.; Osborne, C.K. Significance of axillary lymph node metastasis in primary breast cancer. J. Clin. Oncol. 1999, 17, 2334-2340.
5. Ollila, D.B.; Stitzenberg, K.B. Breast cancer sentinel node metastases: Histopathologic detection and clinical significance. Cancer Control 2001, 8, 407-414.
6. Massucco, P.; Ribero, D.; Sgotto, E.; Mellano, A.; Muratore, A.; Capussotti, L. Prognostic significance of lymph node metastases in pancreatic head cancer treated with extended lymphadenectomy: Not just a matter of numbers. Ann. Surg. Oncol. 2009, 16, 3323-3332.
7. Gervasi, L.A.; Mata, J.; Easley, J.D.; Wilbanks, J.H.; Seale-Hawkins, C.; Carlton, C.E.; Scardino, P.T. Prognostic significance of lymph nodal metastases in prostate cancer. J. Urol. 1989, 142, 332-336.
8. Saito, H.; Fukumoto, Y.; Osaki, T.; Fukuda, K.; Tatebe, S.; Tsujitani, S.; Ikeguchi, M. Prognostic significance of level and number of lymph node metastases in patients with gastric cancer. Ann. Surg. Oncol. 2007, 14, 1688-1693.
9. Willard-Mack, C.L. Normal structure, function, and histology of lymph nodes. Toxicol. Pathol. 2006, 34, 409-424.
10. Beutler, B. Innate immunity: An overview. Mol. Immunol. 2004, 40, 845-859.
11. Kawai, T.; Akira, S. The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat. Immunol. 2010, 11, 373-384.
12. Bonilla, F.A.; Oettgen, H.C. Adaptive immunity. J. Allergy Clin. Immunol. 2010, 125, S33-S40.
13. Von Andrian, U.H.; Mempel, T.R. Homing and cellular traffic in lymph nodes. Nat. Rev. Immunol. 2003, 3, 867-878.
14. Leong, S.P.L.; Nakakura, E.K.; Pollock, R.; Choti, M.A.; Morton, D.L.; Henner, W.D.; Lal, A.; Pillai, R.; Clark, O.H.; Cady, B. Unique patterns of metastases in common and rare types of malignancy. J. Surg. Oncol. 2011, 103, 607-614.
15. Steeg, P.S. Tumor metastasis: Mechanistic insights and clinical challenges. Nat. Med. 2006, 12, 895-904.
16. Hu, M.; Polyak, K. Microenvironmental regulation of cancer development. Curr. Opin. Genet. Dev. 2008, 18, 27-34.
17. Joyce, J.A.; Pollard, J.W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer 2009, 9, 239-252.
18. Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013, 19, 1423-37.
19. Skobe, M.; Hawighorst, T.; Jackson, D.G.; Prevo, R.; Janes, L.; Velasco, P.; Riccardi, L.; Alitalo, K.; Claffey, K.; Detmar, M. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat. Med. 2001, 7, 192-198.
20. Sleeman, J.P.; Thiele, W. Tumor metastasis and the lymphatic vasculature. Int. J. Cancer 2009, 125, 2747-2756.
21. Ran, S.; Volk, L.; Hall, K.; Flister, M.J. Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology 2010, 17, 229-251.
22. Nisato, R.E.; Tille, J.-C.; Pepper, M.S. Lymphangiogenesis and tumor metastasis. Thromb. Haemost. 2003, 90, 591-597.
23. Tobler, N.E.; Detmar, M. Tumor and lymph node lymphangiogenesis-Impact on cancer metastasis. J. Leukoc. Biol. 2006, 80, 691-696.
24. Thiele, W.; Sleeman, J.P. Tumor-induced lymphangiogenesis: A target for cancer therapy? J. Biotechnol. 2006, 124, 224-241.
25. Wissmann, C.; Detmar, M. Pathways targeting tumor lymphangiogenesis. Clin. Cancer Res. 2006, 12, 6865-6868.
26. He, Y.; Kozaki, K.-I.; Karpanen, T.; Koshikawa, K.; Yla-Herttuala, S.; Takahashi, T.; Alitalo, K. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J. Natl. Cancer Inst. 2002, 94, 819-825.
27. Stacker, S.A.; Williams, S.P.; Karnezis, T.; Shayan, R.; Fox, S.B.; Achen, M.G. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat. Rev. Cancer 2014, 14, 159-172.
28. Achen, M.G.; Stacker, S.A. Molecular control of lymphatic metastasis. Ann. N. Y. Acad. Sci. 2008, 1131, 225-234.
29. Nathanson, S.D. Insights into the mechanisms of lymph node metastasis. Cancer 2003, 98, 413-423.
30. Müller, A.; Homey, B.; Soto, H.; Ge, N.; Catron, D.; Buchanan, M.E.; McClanahan, T.; Murphy, E.; Yuan, W.; Wagner, S.N.; et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001, 410, 50-56.
31. Wu, X.; Takekoshi, T.; Sullivan, A.; Hwang, S.T. Inflammation and tumor microenvironment in lymph node metastasis. Cancers 2011, 3, 927-944.
32. Schmid-Schönbein, G.W. Microlymphatics and lymph flow. Physiol. Rev. 1990, 70, 987-1028.
33. Swartz, M.A. The physiology of the lymphatic system. Adv. Drug Deliv. Rev. 2001, 50, 3-20.
34. Rofstad, E.; Tunheim, S.; Mathiesen, B.; Graff, B.; Halsor, E.; Nilsen, K.; Galappathi, K. Pulmonary and lymph node metastasis is associated with primary tumor interstitial fluid pressure in human melanoma xenografts. Cancer Res. 2002, 62, 661-664.
35. Hompland, T.; Ellingsen, C.; Øvrebø, K.M.; Rofstad, E.K. Interstitial fluid pressure and associated lymph node metastasis revealed in tumors by dynamic contrast-enhanced MRI. Cancer Res. 2012, 72, 4899-4908.
36. Moussion, C.; Girard, J.-P. Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules. Nature 2011, 479, 542-546.
37. Mionnet, C.; Sanos, S.L.; Mondor, I.; Jorquera, A.; Laugier, J.-P.; Germain, R.N.; Bajenoff, M. High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes. Blood 2011, 118, 6115-6122.
38. Geng, Y.; Marshall, J.R.; King, M.R. Glycomechanics of the metastatic cascade: Tumor cell-endothelial cell interactions in the circulation. Ann. Biomed. Eng. 2012, 40, 790-805.
39. Sher, B.T.; Bargatze, R.; Holzmann, B.; Gallatin, W.M.; Matthews, D.; Wu, N.; Picker, L.; Butcher, E.C.; Weissman, I.L. Homing receptors and metastasis. Adv. Cancer Res. 1988, 51, 361-390.
40. Bargatze, R.F.; Wu, N.W.; Weissman, I.L.; Butcher, E.C. High endothelial venule binding as a predictor of the dissemination of passaged murine lymphomas. J. Exp. Med. 1987, 166, 1125-1131.
41. Ozcinar, B.; Muslumanoglu, M.; Igci, A.; Gurdal, S.O.; Yavuz, E.; Kecer, M.; Dagoglu, T.; Ozmen, V. Clinical importance of micrometastasis in sentinel lymph nodes. Breast 2011, 20, 31-33.
42. Mehes, G.; Witt, A.; Kubista, E.; Ambros, P.F. Classification of isolated tumor cells and micrometastasis. Cancer 2000, 89, 709-711.
43. Noura, S.; Yamamoto, H.; Miyake, Y.; Kim, B.N.; Takayama, O.; Seshimo, I.; Ikenaga, M.; Ikeda, M.; Sekimoto, M.; Matsuura, N.; et al. Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer. Clin. Cancer Res. 2002, 8, 759-767.
44. Weaver, D.L.; Krag, D.N.; Manna, E.A.; Ashikaga, T.; Waters, B.L.; Harlow, S.P.; Bauer, K.D.; Julian, T.B. Detection of occult sentinel lymph node micrometastases by immunohistochemistry in breast cancer. An NSABP protocol B-32 quality assurance study. Cancer 2006, 107, 661-667.
45. Gerber, B.; Krause, A.; Muller, H.; Richter, D.; Reimer, T.; Makovitzky, J.; Herrnring, C.; Jeschke, U.; Kundt, G.; Friese, K. Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors. J. Clin. Oncol. 2001, 19, 960-971.
46. Mori, M.; Mimori, K.; Inoue, H.; Barnard, G.F.; Tsuji, K.; Nanbara, S.; Ueo, H.; Akiyoshi, T. Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res. 1995, 55, 3417-3420.
47. Slade, M.J.; Smith, B.M.; Sinnett, H.D.; Cross, N.C.; Coombes, R.C. Quantitative polymerase chain reaction for the detection of micrometastases in patients with breast cancer. J. Clin. Oncol. 1999, 17, 870-879.
48. Sahai, E. Illuminating the metastatic process. Nat. Rev. Cancer 2007, 7, 737-749.
49. Rosenberg, S.A. Progress in human tumour immunology and immunotherapy. Nature 2001, 411, 380-384.
50. Munn, D.H.; Mellor, A.L. The tumor-draining lymph node as an immune-privileged site. Immunol. Rev. 2006, 213, 146-158.
51. Shu, S.; Cochran, A.J.; Huang, R.-R.; Morton, D.L.; Maecker, H.T. Immune responses in the draining lymph nodes against cancer: Implications for immunotherapy. Cancer Metastasis Rev. 2006, 25, 233-242.
52. Fransen, M.F.; Arens, R.; Melief, C.J.M. Local targets for immune therapy to cancer: Tumor draining lymph nodes and tumor microenvironment. Int. J. Cancer 2013, 132, 1971-1976.
53. Jeanbart, L.; Ballester, M.; de Titta, A.; Corthesy, P.; Romero, P.; Hubbell, J.A.; Swartz, M.A. Enhancing efficacy of anti-cancer vaccines by targeted delivery to tumor-draining lymph nodes. Cancer Immunol. Res. 2014, doi:10.1158/2326-6066.CIR-14-0019-T.
54. Thomas, S.N.; Vokali, E.; Lund, A.W.; Hubbell, J.A.; Swartz, M.A. Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response. Biomaterials 2014, 35, 814-824.
55. Sixt, M.; Kanazawa, N.; Selg, M.; Samson, T.; Roos, G.; Reinhardt, D.P.; Pabst, R.; Lutz, M.B.; Sorokin, L. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 2005, 22, 19-29.
56. Roozendaal, R.; Mebius, R.E.; Kraal, G. The conduit system of the lymph node. Int. Immunol. 2008, 20, 1483-1487.
57. Lee, S.; Margolin, K. Tumor-infiltrating lymphocytes in melanoma. Curr. Oncol. Rep. 2012, 14, 468-474.
58. Yu, P.; Fu, Y.-X. Tumor-infiltrating T lymphocytes: Friends or foes? Lab. Investig. 2006, 86, 231-245.
59. Lança, T.; Silva-Santos, B. The split nature of tumor-infiltrating leukocytes: Implications for cancer surveillance and immunotherapy. Oncoimmunology 2012, 1, 717-725.
60. Zhang, J.-Y.; Looi, K.S.; Tan, E.M. Identification of tumor-associated antigens as diagnostic and predictive biomarkers in cancer. Methods Mol. Biol. 2009, 520, 1-10.
61. Pardoll, D. T cells take aim at cancer. Proc. Natl. Acad. Sci. USA 2002, 99 , 15840-15842.
62. Shankaran, V.; Ikeda, H.; Bruce, A.T.; White, J.M.; Swanson, P.E.; Old, L.J.; Schreiber, R.D. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001, 410, 1107-1111.
63. Smyth, M.J.; Thia, K.Y.; Street, S.E.; MacGregor, D.; Godfrey, D.I.; Trapani, J.A. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J. Exp. Med. 2000, 192, 755-760.
64. Swann, J.B.; Smyth, M.J. Immune surveillance of tumors. J. Clin. Investig. 2007, 117, 1137-1146.
65. Dunn, G.P.; Bruce, A.T.; Ikeda, H.; Old, L.J.; Schreiber, R.D. Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol. 2002, 3, 991-998.
66. Dunn, G.P.; Old, L.J.; Schreiber, R.D. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004, 21, 137-148.
67. Wu, J.; Lanier, L.L. Natural killer cells and cancer. Adv. Cancer Res. 2003, 90, 127-156.
68. Cheent, K.; Khakoo, S.I. Natural killer cells: Integrating diversity with function. Immunology 2009, 126, 449-457.
69. Orange, J.S.; Ballas, Z.K. Natural killer cells in human health and disease. Clin. Immunol. 2006, 118, 1-10.
70. Koch, J.; Steinle, A.; Watzl, C.; Mandelboim, O. Activating natural cytotoxicity receptors of natural killer cells in cancer and infection. Trends Immunol. 2013, 34, 182-191.
71. Zamai, L.; Ahmad, M.; Bennett, I.M.; Azzoni, L.; Alnemri, E.S.; Perussia, B. Natural Killer (NK) cell-mediated cytotoxicity: Differential use of TRAIL and fas ligand by immature and mature primary human NK cells. J. Exp. Med. 1998, 188, 2375-2380.
72. Hicklin, D.J.; Marincola, F.M.; Ferrone, S. HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol. Med. Today 1999, 5, 178-186.
73. Aptsiauri, N.; Cabrera, T.; Mendez, R.; Garcia-Lora, A.; Ruiz-Cabello, F.; Garrido, F. Role of altered expression of HLA class I molecules in cancer progression. Adv. Exp. Med. Biol. 2007, 601, 123-131.
74. Smyth, M.J.; Crowe, N.Y.; Godfrey, D.I. NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int. Immunol. 2001, 13, 459-463.
75. Smyth, M.J.; Cretney, E.; Takeda, K.; Wiltrout, R.H.; Sedger, L.M.; Kayagaki, N.; Yagita, H.; Okumura, K. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J. Exp. Med. 2001, 193, 661-670.
76. Caligiuri, M.A. Human natural killer cells. Blood 2008, 112, 461-469.
77. Morris, M.A.; Ley, K. Trafficking of natural killer cells. Curr. Mol. Med. 2004, 4, 431-438.
78. Levy, E.M.; Roberti, M.P.; Mordoh, J. Natural killer cells in human cancer: From biological functions to clinical applications. J. Biomed. Biotechnol. 2011, 2011, 676198.
79. Martín-Fontecha, A.; Thomsen, L.L.; Brett, S.; Gerard, C.; Lipp, M.; Lanzavecchia, A.; Sallusto, F. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat. Immunol. 2004, 5, 1260-1265.
80. Ferlazzo, G.; Thomas, D.; Lin, S.-L.; Goodman, K.; Morandi, B.; Muller, W.A.; Moretta, A.; Münz, C. The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. J. Immunol. 2004, 172, 1455-1462.
81. Garrod, K.R.; Wei, S.H.; Parker, I.; Cahalan, M.D. Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets. Proc. Natl. Acad. Sci. USA 2007, 104, 12081-12086.
82. Fehniger, T.A.; Cooper, M.A.; Nuovo, G.J.; Cella, M.; Facchetti, F.; Colonna, M.; Caligiuri, M.A. CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: A potential new link between adaptive and innate immunity. Blood 2003, 101, 3052-3057.
83. Bajénoff, M.; Breart, B.; Huang, A.Y.C.; Qi, H.; Cazareth, J.; Braud, V.M.; Germain, R.N.; Glaichenhaus, N. Natural killer cell behavior in lymph nodes revealed by static and real-time imaging. J. Exp. Med. 2006, 203, 619-631.
84. Messaoudene, M.; Fregni, G.; Fourmentraux-Neves, E.; Chanal, J.; Maubec, E.; Mazouz-Dorval, S.; Couturaud, B.; Girod, A.; Sastre-Garau, X.; Albert, S.; et al. Ge mature cytotoxic CD56bright/CD16+ natural killer cells can infiltrate lymph nodes adjacent to metastatic melanoma. Cancer Res. 2014, 74, 81-92.
85. Baskic, D.; Vujanovic, L.; Arsenijevic, N.; Whiteside, T.L.; Myers, E.N.; Vujanovic, N.L. Suppression of natural killer-cell and dendritic-cell apoptotic tumoricidal activity in patients with head and neck cancer. Head Neck 2013, 35, 388-398.
86. Mamessier, E.; Sylvain, A.; Thibult, M.-L.; Houvenaeghel, G.; Jacquemier, J.; Castellano, R.; Gonçalves, A.; André, P.; Romagné, F.; Thibault, G.; et al. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J. Clin. Investig. 2011, 121, 3609-3622.
87. Doubrovina, E.S.; Doubrovin, M.M.; Vider, E.; Sisson, R.B.; O'Reilly, R.J.; Dupont, B.; Vyas, Y.M. Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J. Immunol. 2003, 171, 6891-6899.
88. Hersey, P.; Zhang, X.D. How melanoma cells evade trail-induced apoptosis. Nat. Rev. Cancer 2001, 1, 142-150.
89. Van Mierlo, G.J.D.; Boonman, Z.F.H.M.; Dumortier, H.M.H.; den Boer, A.T.; Fransen, M.F.; Nouta, J.; van der Voort, E.I.H.; Offringa, R.; Toes, R.E.M.; Melief, C.J.M. Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication. J. Immunol. 2004, 173, 6753-6759.
90. Engelhardt, J.J.; Boldajipour, B.; Beemiller, P.; Pandurangi, P.; Sorensen, C.; Werb, Z.; Egeblad, M.; Krummel, M.F. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell 2012, 21, 402-417.
91. Yu, P.; Spiotto, M.T.; Lee, Y.; Schreiber, H.; Fu, Y.-X. Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigen to CD8+ T cells. J. Exp. Med. 2003, 197, 985-995.
92. Nagorsen, D.; Scheibenbogen, C.; Marincola, F.M.; Letsch, A.; Keilholz, U. Natural T cell immunity against cancer. Clin. Cancer Res. 2003, 9, 4296-4303.
93. Petersen, T.R.; Dickgreber, N.; Hermans, I.F. Tumor antigen presentation by dendritic cells. Crit. Rev. Immunol. 2010, 30, 345-386.
94. Hung, K.; Hayashi, R.; Lafond-Walker, A.; Lowenstein, C.; Pardoll, D.; Levitsky, H. The central role of CD4(+) T cells in the antitumor immune response. J. Exp. Med. 1998, 188, 2357-2368.
95. Corthay, A.; Skovseth, D.K.; Lundin, K.U.; Røsjø, E.; Omholt, H.; Hofgaard, P.O.; Haraldsen, G.; Bogen, B. Primary antitumor immune response mediated by CD4+ T cells. Immunity 2005, 22, 371-383.
96. Rizzuto, G.A.; Merghoub, T.; Hirschhorn-Cymerman, D.; Liu, C.; Lesokhin, A.M.; Sahawneh, D.; Zhong, H.; Panageas, K.S.; Perales, M.-A.; Altan-Bonnet, G.; et al. Self-antigen-specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response. J. Exp. Med. 2009, 206, 849-866.
97. Nakayama, H.; Kitayama, J.; Muto, T.; Nagawa, H. Characterization of intracellular cytokine profile of CD4(+) T cells in peripheral blood and tumor-draining lymph nodes of patients with gastrointestinal cancer. Jpn. J. Clin. Oncol. 2000, 30, 301-305.
98. Lee, J.H.; Torisu-Itakara, H.; Cochran, A.J.; Kadison, A.; Huynh, Y.; Morton, D.L.; Essner, R. Quantitative analysis of melanoma-induced cytokine-mediated immunosuppression in melanoma sentinel nodes. Clin. Cancer Res. 2005, 11, 107-112.
99. Yang, Y.; Huang, C.-T.; Huang, X.; Pardoll, D.M. Persistent toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat. Immunol. 2004, 5, 508-515.
100. Wang, R.F. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum. Immunol. 2008, 69, 811-814.
101. Liu, Z.; Kim, J.H.; Falo, L.D.; You, Z. Tumor regulatory T cells potently abrogate antitumor immunity. J. Immunol. 2009, 182, 6160-6167.
102. James, E.; Yeh, A.; King, C.; Korangy, F.; Bailey, I.; Boulanger, D.S.; van den Eynde, B.J.; Murray, N.; Elliott, T.J. Differential suppression of tumor-specific CD8+ T cells by regulatory T cells. J. Immunol. 2010, 185, 5048-5055.
103. Grauer, O.M.; Nierkens, S.; Bennink, E.; Toonen, L.W.J.; Boon, L.; Wesseling, P.; Sutmuller, R.P.M.; Adema, G.J. CD4+ FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int. J. Cancer 2007, 121, 95-105.
104. Kiniwa, Y.; Miyahara, Y.; Wang, H.Y.; Peng, W.; Peng, G.; Wheeler, T.M.; Thompson, T.C.; Old, L.J.; Wang, R.-F. CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin. Cancer Res. 2007, 13, 6947-6958.
105. Chen, M.-L.; Pittet, M.J.; Gorelik, L.; Flavell, R.A.; Weissleder, R.; von Boehmer, H.; Khazaie, K. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc. Natl. Acad. Sci. USA 2005, 102, 419-424.
106. Viehl, C.T.; Moore, T.T.; Liyanage, U.K.; Frey, D.M.; Ehlers, J.P.; Eberlein, T.J.; Goedegebuure, P.S.; Linehan, D.C. Depletion of CD4+ CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice. Ann. Surg. Oncol. 2006, 13, 1252-1258.
107. Dercamp, C.; Chemin, K.; Caux, C.; Trinchieri, G.; Vicari, A.P. Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses. Cancer Res. 2005, 65, 8479-8486.
108. Peng, L.; Kjaergäard, J.; Plautz, G.E.; Awad, M.; Drazba, J.A.; Shu, S.; Cohen, P.A. Tumor-induced L-selectin high suppressor T cells mediate potent effector T cell blockade and cause failure of otherwise curative adoptive immunotherapy. J. Immunol. 2002, 169, 4811-4821.
109. Jarnicki, A.G.; Lysaght, J.; Todryk, S.; Mills, K.H.G. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: Influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J. Immunol. 2006, 177, 896-904.
110. Ma, Y.; Shurin, G.V; Peiyuan, Z.; Shurin, M.R. Dendritic cells in the cancer microenvironment. J. Cancer 2013, 4, 36-44.
111. Srinivasan, R.; Wolchok, J.D. Tumor antigens for cancer immunotherapy: Therapeutic potential of xenogeneic DNA vaccines. J. Transl. Med. 2004, 2, 12.
112. McDonnell, A.M.; Robinson, B.W.S.; Currie, A.J. Tumor antigen cross-presentation and the dendritic cell: Where it all begins? Clin. Dev. Immunol. 2010, 2010, 539519.
113. Joshi, M.D.; Unger, W.J.; Storm, G.; van Kooyk, Y.; Mastrobattista, E. Targeting tumor antigens to dendritic cells using particulate carriers. J. Control. Release 2012, 161, 25-37.
114. Cochran, A.J.; Morton, D.L.; Stern, S.; Lana, A.M.; Essner, R.; Wen, D.R. Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: Implications for tumor biology and treatment. Mod. Pathol. 2001, 14, 604-608.
115. Almand, B.; Resser, J.R.; Lindman, B.; Nadaf, S.; Clark, J.I.; Kwon, E.D.; Carbone, D.P.; Gabrilovich, D.I. Clinical significance of defective dendritic cell differentiation in cancer. Clin. Cancer Res. 2000, 6, 1755-1766.
116. Harris, N.L.; Ronchese, F. The role of B7 costimulation in T-cell immunity. Immunol. Cell Biol. 1999, 77, 304-311.
117. Grewal, I.S.; Flavell, R.A. The role of CD40 ligand in costimulation and T-cell activation. Immunol. Rev. 1996, 153, 85-106.
118. Shuford, W.W.; Klussman, K.; Tritchler, D.D.; Loo, D.T.; Chalupny, J.; Siadak, A.W.; Brown, T.J.; Emswiler, J.; Raecho, H.; Larsen, C.P.; et al. 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J. Exp. Med. 1997, 186, 47-55.
119. Scholer, A.; Hugues, S.; Boissonnas, A.; Fetler, L.; Amigorena, S. Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory. Immunity 2008, 28, 258-270.
120. Hargadon, K.M. Tumor-altered dendritic cell function: Implications for anti-tumor immunity. Front. Immunol. 2013, 4, 192.
121. Munn, D.H.; Sharma, M.D.; Hou, D.; Baban, B.; Lee, J.R.; Antonia, S.J.; Messina, J.L.; Chandler, P.; Koni, P.A.; Mellor, A.L. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J. Clin. Investig. 2004, 114, 280-290.
122. Sharma, M.D.; Baban, B.; Chandler, P.; Hou, D.-Y.; Singh, N.; Yagita, H.; Azuma, M.; Blazar, B.R.; Mellor, A.L.; Munn, D.H. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J. Clin. Investig. 2007, 117, 2570-2582.
123. Cochran, A.J.; Huang, R.-R.; Itakura, E.; Lee, J.H.; Molenkamp, B.G. Dendritic Cells in Tumor-Draining Lymph Nodes; Salter, R.D., Shurin, M.R., Eds.; Springer: New York, NY, USA, 2009; pp. 291-307.
124. Fremd, C.; Schuetz, F.; Sohn, C.; Beckhove, P.; Domschke, C. B cell-regulated immune responses in tumor models and cancer patients. Oncoimmunology 2013, 2, e25443.
125. Coronella-Wood, J.A.; Hersh, E.M. Naturally occurring B-cell responses to breast cancer. Cancer Immunol. Immunother. 2003, 52, 715-738.
126. Li, Q.; Grover, A.C.; Donald, E.J.; Carr, A.; Yu, J.; Whitfield, J.; Nelson, M.; Takeshita, N.; Chang, A.E. Simultaneous targeting of CD3 on T cells and CD40 on B or dendritic cells augments the antitumor reactivity of tumor-primed lymph node cells. J. Immunol. 2005, 175, 1424-1432.
127. Marits, P.; Zirakzadeh, A.A; Sherif, A.; Winqvist, O. The many flavors of tumor-associated B cells. Oncoimmunology 2013, 2, e25237.
128. Zirakzadeh, A.A.; Marits, P.; Sherif, A.; Winqvist, O. Multiplex B cell characterization in blood, lymph nodes, and tumors from patients with malignancies. J. Immunol. 2013, 190, 5847-5855.
129. Shimabukuro-Vornhagen, A.; Schlößer, H.A.; Stippel, D.L.; Theurich, S.; von Bergwelt-Baildon, M. Comment on "Multiplex B cell characterization in blood, lymph nodes, and tumors from patients with malignancies." J. Immunol. 2013, 191, 4471.
130. Marits, P.; Zirakzadeh, A.A.; Sherif, A.; Winqvist, O. Response to comment on "Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies." J. Immunol. 2013, 191, 4471-4472.
131. Kim, R.; Emi, M.; Tanabe, K. Cancer immunoediting from immune surveilance to immune escape. Immunology 2007, 121, 1-14.
132. Kim, R.; Emi, M.; Tanabe, K.; Arihiro, K. Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res. 2006, 66, 5527-5536.
133. Hood, J.L.; San Roman, S.; Wickline, S.A. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011, 71, 3792-3801.
134. Mansfield, A.S.; Holtan, S.G.; Grotz, T.E.; Allred, J.B.; Jakub, J.W.; Erickson, L.A.; Markovic, S.N. Regional immunity in melanoma: Immunosuppressive changes precede nodal metastasis. Mod. Pathol. 2011, 24, 487-494.
135. Zuckerman, N.S.; Yu, H.; Simons, D.L.; Bhattacharya, N.; Carcamo-Cavazos, V.; Yan, N.; Dirbas, F.M.; Johnson, D.L.; Schwartz, E.J.; Lee, P.P. Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients. Int. J. Cancer 2013, 132, 2537-2547.
136. Banchereau, J.; Palucka, A.K. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol. 2005, 5, 296-306.
137. Sabado, R.L.; Bhardwaj, N. Directing dendritic cell immunotherapy towards successful cancer treatment. Immunotherapy 2010, 2, 37-56.
138. Melief, C.J.M. Cancer immunotherapy by dendritic cells. Immunity 2008, 29, 372-383.
139. Schuler, G. Dendritic cells in cancer immunotherapy. Eur. J. Immunol. 2010, 40, 2123-2130.
140. Palucka, K.; Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer 2012, 12, 265-277.
141. Boudreau, J.E.; Bonehill, A.; Thielemans, K.; Wan, Y. Engineering dendritic cells to enhance cancer immunotherapy. Mol. Ther. 2011, 19, 841-853.
142. Mak, I.W.; Evaniew, N.G.M. Lost in translation: Animal models and clinical trials in cancer treatment. Am. J. Transl. Res. 2014, 6, 114-118.
143. Bhatia, S.; Tykodi, S.S.; Thompson, J.A. Treatment of metastatic melanoma: An overview. Oncology 2009, 23, 488-496.
144. Rosenberg, S.A.; Packard, B.S.; Aebersold, P.M.; Solomon, D.; Topalian, S.L.; Toy, S.T.; Simon, P.; Lotze, M.T.; Yang, J.C.; Seipp, C.A. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 1988, 319, 1676-1680.
145. Dillman, R.O.; Barth, N.M.; VanderMolen, L.A.; Mahdavi, K.; McClure, S.E. Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic melanoma? Cancer Biother. Radiopharm. 2012, 27, 337-343.
146. Rosenberg, S.A.; Yang, J.C.; Restifo, N.P. Cancer immunotherapy: Moving beyond current vaccines. Nat. Med. 2004, 10, 909-915.
147. Parmiani, G.; Castelli, C.; Dalerba, P.; Mortarini, R.; Rivoltini, L.; Marincola, F.M.; Anichini, A. Cancer immunotherapy with peptide-based vaccines: What have we achieved? Where are we going? J. Natl. Cancer Inst. 2002, 94, 805-818.
148. Kwon, E.D.; Hurwitz, A.A.; Foster, B.A.; Madias, C.; Feldhaus, A.L.; Greenberg, N.M.; Burg, M.B.; Allison, J.P. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl. Acad. Sci. USA 1997, 94, 8099-8103.
149. Berger, T.G.; Schultz, E.S. Dendritic cell-based immunotherapy. Curr. Top. Microbiol. Immunol. 2003, 276, 163-197.
150. Fernandez, N.; Duffour, M.T.; Perricaudet, M.; Lotze, M.T.; Tursz, T.; Zitvogel, L. Active specific T-cell-based immunotherapy for cancer: Nucleic acids, peptides, whole native proteins, recombinant viruses, with dendritic cell adjuvants or whole tumor cell-based vaccines. Principles and future prospects. Cytokines Cell Mol. Ther. 1998, 4, 53-65.
151. Paulis, L.E.; Mandal, S.; Kreutz, M.; Figdor, C.G. Dendritic cell-based nanovaccines for cancer immunotherapy. Curr. Opin. Immunol. 2013, 25, 389-395.
152. Jesorka, A.; Orwar, O. Liposomes: Technologies and analytical applications. Annu. Rev. Anal. Chem. 2008, 1, 801-832.
153. Čeh, B.; Winterhalter, M.; Frederik, P.M.; Vallner, J.J.; Lasic, D.D. Stealth® liposomes: From theory to product. Adv. Drug Deliv. Rev. 1997, 24, 165-177.
154. Oussoren, C.; Storm, G. Liposomes to target the lymphatics by subcutaneous administration. Adv. Drug Deliv. Rev. 2001, 50, 143-156.
155. Phillips, W.T.; Goins, B.A.; Medina, L.A. Targeting of liposomes to lymph nodes. In Liposome Technology; Informa Healthcare: New York, NY, USA, 2006; Volume 3, pp. 13-231.
156. Altin, J.G.; Parish, C.R. Liposomal vaccines-targeting the delivery of antigen. Methods 2006, 40, 39-52.
157. Fleiner, M.; Benzinger, P.; Fichert, T.; Massing, U. Studies on protein-liposome coupling using novel thiol-reactive coupling lipids: Influence of spacer length and polarity. Bioconjug. Chem. 2001, 12, 470-475.
158. Van Broekhoven, C.L.; Altin, J.G. A novel system for convenient detection of low-affinity receptor-ligand interactions: Chelator-lipid liposomes engrafted with recombinant CD4 bind to cells expressing MHC class II. Immunol. Cell Biol. 2001, 79, 274-284.
159. Foged, C.; Arigita, C.; Sundblad, A.; Jiskoot, W.; Storm, G.; Frokjaer, S. Interaction of dendritic cells with antigen-containing liposomes: Effect of bilayer composition. Vaccine 2004, 22, 1903-1913.
160. Van Broekhoven, C.L.; Parish, C.R.; Demangel, C.; Britton, W.J.; Altin, J.G. Targeting dendritic cells with antigen-containing liposomes: A highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 2004, 64, 4357-4365.
161. Storni, T.; Kündig, T.M.; Senti, G.; Johansen, P. Immunity in response to particulate antigen-delivery systems. Adv. Drug Deliv. Rev. 2005, 57, 333-355.
162. Ikehara, Y.; Niwa, T.; Biao, L.; Ikehara, S.K.; Ohashi, N.; Kobayashi, T.; Shimizu, Y.; Kojima, N.; Nakanishi, H. A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle. Cancer Res. 2006, 66, 8740-8748.
163. Ikehara, Y.; Shiuchi, N.; Kabata-Ikehara, S.; Nakanishi, H.; Yokoyama, N.; Takagi, H.; Nagata, T.; Koide, Y.; Kuzushima, K.; Takahashi, T.; et al. Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells. Cancer Lett. 2008, 260, 137-145.
164. Kojima, N.; Biao, L.; Nakayama, T.; Ishii, M.; Ikehara, Y.; Tsujimura, K. Oligomannose-coated liposomes as a therapeutic antigen-delivery and an adjuvant vehicle for induction of in vivo tumor immunity. J. Control. Release 2008, 129, 26-32.
165. Kojima, N.; Ishii, M.; Kawauchi, Y.; Takagi, H. Oligomannose-coated liposome as a novel adjuvant for the induction of cellular immune responses to control disease status. Biomed. Res. Int. 2013, 2013, 562924.
166. Elgueta, R.; Benson, M.J.; de Vries, V.C.; Wasiuk, A.; Guo, Y.; Noelle, R.J. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 2009, 229, 152-172.
167. French, R.R.; Chan, H.T.; Tutt, A.L.; Glennie, M.J. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat. Med. 1999, 5, 548-553.
168. Tutt, A.L.; O'Brien, L.; Hussain, A.; Crowther, G.R.; French, R.R.; Glennie, M.J. T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody. J. Immunol. 2002, 168, 2720-2728.
169. Vonderheide, R.H.; Flaherty, K.T.; Khalil, M.; Stumacher, M.S.; Bajor, D.L.; Hutnick, N.A.; Sullivan, P.; Mahany, J.J.; Gallagher, M.; Kramer, A.; et al. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J. Clin. Oncol. 2007, 25, 876-883.
170. Krieg, A.M. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene 2008, 27, 161-167.
171. Krieg, A.M. Development of TLR9 agonists for cancer therapy. J. Clin. Investig. 2007, 117, 1184-1194.
172. Heikenwalder, M.; Polymenidou, M.; Junt, T.; Sigurdson, C.; Wagner, H.; Akira, S.; Zinkernagel, R.; Aguzzi, A. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat. Med. 2004, 10, 187-192.
173. Kwong, B.; Liu, H.; Irvine, D.J. Induction of potent anti-tumor responses while eliminating systemic side effects via liposome-anchored combinatorial immunotherapy. Biomaterials 2011, 32, 5134-5147.
174. Karanth, H.; Murthy, R.S.R. pH-sensitive liposomes-Principle and application in cancer therapy. J. Pharm. Pharmacol. 2007, 59, 469-483.
175. Yuba, E.; Harada, A.; Sakanishi, Y.; Watarai, S.; Kono, K. A liposome-based antigen delivery system using pH-sensitive fusogenic polymers for cancer immunotherapy. Biomaterials 2013, 34, 3042-3052.
176. Yuba, E.; Tajima, N.; Yoshizaki, Y.; Harada, A.; Hayashi, H.; Kono, K. Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy. Biomaterials 2014, 35, 3091-3101.
177. Leitner, J.; Grabmeier-Pfistershammer, K.; Steinberger, P. Receptors and ligands implicated in human T cell costimulatory processes. Immunol. Lett. 2010, 128, 89-97.
178. Leitner, J.; Kuschei, W.; Grabmeier-Pfistershammer, K.; Woitek, R.; Kriehuber, E.; Majdic, O.; Zlabinger, G.; Pickl, W.F.; Steinberger, P. T cell stimulator cells, an efficient and versatile cellular system to assess the role of costimulatory ligands in the activation of human T cells. J. Immunol. Methods 2010, 362, 131-141.
179. Kwong, B.; Gai, S.A.; Elkhader, J.; Wittrup, K.D.; Irvine, D.J. Localized Immunotherapy via liposome-anchored anti-CD137 + IL-2 prevents lethal toxicity and elicits local and systemic antitumor immunity. Cancer Res. 2013, 73, 1547-1558.
180. Vinay, D.S.; Kwon, B.S. Immunotherapy of cancer with 4-1BB. Mol. Cancer Ther. 2012, 11, 1062-1070.
181. Melero, I.; Shuford, W.W.; Newby, S.A.; Aruffo, A.; Ledbetter, J.A.; Hellström, K.E.; Mittler, R.S.; Chen, L. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat. Med. 1997, 3, 682-685.
182. Atkins, M.B.; Lotze, M.T.; Dutcher, J.P.; Fisher, R.I.; Weiss, G.; Margolin, K.; Abrams, J.; Sznol, M.; Parkinson, D.; Hawkins, M.; et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993. J. Clin. Oncol. 1999, 17, 2105-2116.
183. Phan, G.Q.; Attia, P.; Steinberg, S.M.; White, D.E.; Rosenberg, S.A. Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J. Clin. Oncol. 2001, 19, 3477-3482.
184. Rosenberg, S.A.; Lotze, M.T.; Muul, L.M.; Chang, A.E.; Avis, F.P.; Leitman, S.; Linehan, W.M.; Robertson, C.N.; Lee, R.E.; Rubin, J.T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N. Engl. J. Med. 1987, 316, 889-897.
185. Zheng, Y.; Stephan, M.T.; Gai, S.A.; Abraham, W.; Shearer, A.; Irvine, D.J. In vivo targeting of adoptively transferred T-cells with antibody- and cytokine-conjugated liposomes. J. Control. Release 2013, 172, 426-435.
186. Zamai, L.; Ponti, C.; Mirandola, P.; Gobbi, G.; Papa, S.; Galeotti, L.; Cocco, L.; Vitale, M. NK cells and cancer. J. Immunol. 2007, 178, 4011-4016.
187. Chandrasekaran, S.; McGuire, M.J.; King, M.R. Sweeping lymph node micrometastases off their feet: An engineered model to evaluate natural killer cell mediated therapeutic intervention of circulating tumor cells that disseminate to the lymph nodes. Lab Chip 2014, 14, 118-127.
188. Xiang, H.; Nguyen, C.B.; Kelley, S.K.; Dybdal, N.; Escand, E. Tissue distribution, stability, and pharmacokinetics of Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in human colon carcinoma COLO205 tumor-bearing nude mice. Pharmacology 2004, 32, 1230-1238.
189. Cheng, M.; Chen, Y.; Xiao, W.; Sun, R.; Tian, Z. NK cell-based immunotherapy for malignant diseases. Cell Mol. Immunol. 2013, 10, 230-252.
190. Mitchell, M.J.; Wayne, E.; Rana, K.; Schaffer, C.B.; King, M.R. TRAIL-coated leukocytes that kill cancer cells in the circulation. Proc. Natl. Acad. Sci. USA 2014, 113, 930-935.
191. Muller, W.A. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 2003, 24, 326-333.
192. Zarbock, A.; Ley, K.; McEver, R.P.; Hidalgo, A. Leukocyte ligands for endothelial selectins: Specialized glycoconjugates that mediate rolling and signaling under flow. Blood 2011, 118, 6743-6751.
193. Mitchell, M.J.; King, M.R. Physical biology in cancer. 3. The role of cell glycocalyx in vascular transport of circulating tumor cells. Am. J. Physiol. Cell Physiol. 2014, 306, C89-C97.