Harnessing the Microbiome to Enhance Cancer Immunotherapy

Journal of Immunology Research

Volumn 2015, Issue , 2015, Pages

  Nelson, Michelle H ^a   Diven, Marshall A ^a   Huff, Logan W ^a   Paulos, Chrystal M ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER VACCINE; CYTOKINE; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR AGONIST; BACTERIAL TOXIN;

ADAPTIVE IMMUNITY; ADOPTIVE IMMUNOTHERAPY; ANTINEOPLASTIC ACTIVITY; CANCER ADJUVANT THERAPY; CANCER CELL; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER THERAPY; CD4+ T LYMPHOCYTE; COMMENSAL; EXPERIMENTAL THERAPY; HUMAN; INNATE IMMUNITY; INTESTINE FLORA; MEMORY T LYMPHOCYTE; MICROBIOME; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; T CELL DEPLETION; TH17 CELL; TUMOR IMMUNITY; TUMOR REGRESSION; ADJUVANT CHEMOTHERAPY; ANIMAL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; IMMUNOMODULATION; IMMUNOTHERAPY; LYMPHOCYTE DEPLETION; METABOLISM; MICROFLORA; NEOPLASMS; PATHOLOGY; PROCEDURES; T LYMPHOCYTE; WHOLE BODY RADIATION;

ADAPTIVE IMMUNITY; ANIMALS; BACTERIAL TOXINS; CANCER VACCINES; CHEMOTHERAPY, ADJUVANT; CYTOKINES; GASTROINTESTINAL MICROBIOME; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNITY, INNATE; IMMUNOMODULATION; IMMUNOTHERAPY; IMMUNOTHERAPY, ADOPTIVE; LYMPHOCYTE DEPLETION; MICROBIOTA; NEOPLASMS; T-LYMPHOCYTES; TOLL-LIKE RECEPTORS; WHOLE-BODY IRRADIATION;

EID: 84935900620     PISSN: 23148861     EISSN: 23147156     Source Type: Journal    
DOI: 10.1155/2015/368736     Document Type: Review

References (148)

1. Human Microbiome Project Consortium, "Structure, function and diversity of the healthy human microbiome, " Nature, vol. 486, pp. 207-214, 2012.
2. E. Biagi, M. Cand ela, S. Turroni, P. Garagnani, C. Franceschi, and P. Brigidi, "Ageing and gut microbes: perspectives for health maintenance and longevity, " Pharmacological Research, vol. 69, no. 1, pp. 11-20, 2013.
3. C. Lupp, M. Skipper, and U. Weiss, "Gut microbes and health, " Nature, vol. 489, no. 7415, p. 219, 2012.
4. L. V. Hooper, M. H. Wong, A. Thelin, L. Hansson, P. G. Falk, and J. I. Gordon, "Molecular analysis of commensal host-microbial relationships in the intestine, " Science, vol. 291, no. 5505, pp. 881-884, 2001.
5. M. J. Mcfall-Ngai and E. G. Ruby, "Symbiont recognition and subsequent morphogenesis as early events in an animalbacterial mutualism, " Science, vol. 254, no. 5037, pp. 1491-1494, 1991.
6. C. M. Paulos, C. Wrzesinski, A. Kaiser, et al., "Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling, " Journal of Clinical Investigation, vol. 117, no. 8, pp. 2197-2204, 2007.
7. R. R. Jenq, C. Ubeda, Y. Taur, et al., "Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation, "The Journal of ExperimentalMedicine, vol. 209, no. 5, pp. 903-911, 2012.
8. D. N. Frank, A. L. St. Amand, R. A. Feldman, E. C. Boedeker, N. Harpaz, and N. R. Pace, "Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases, " Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 34, pp. 13780-13785, 2007.
9. C. M. Paulos, A. Kaiser, C. Wrzesinski, et al., "Toll-like receptors in tumor immunotherapy, " Clinical Cancer Research, vol. 13, no. 18, pp. 5280-5289, 2007.
10. B. Wiemann and C. O. Starnes, "Coleys toxins, tumor necrosis factor and cancer research: a historical perspective, " Pharmacology and Therapeutics, vol. 64, no. 3, pp. 529-564, 1994.
11. C. O. Starnes, "Coleys toxins in perspective, " Nature, vol. 357, no. 6373, pp. 11-12, 1992.
12. W. Coley, The Treatment of Malignant Inoperable Tumors in the Mixed Toxins of Erysipelas and Bacillus Prodigiosus, M. Weissenbruch, Brussels, Belgium, 1914.
13. E. F. McCarthy, "The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas, " The Iowa Orthopaedic Journal, vol. 26, pp. 154-158, 2006.
14. H. C. Nauts, G. A. Fowler, and F. H. Bogatko, "A review of the influence of bacterial infection and of bacterial products (Coleys toxins) on malignant tumors in man; a critical analysis of 30 inoperable cases treated by Coleys mixed toxins, in which diagnosis was confirmed by microscopic examination selected for special study, " Acta medica Scand inavica. Supplementum, vol. 276, pp. 1-103, 1953.
15. W. B. Coley, "The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases, " Clinical Orthopaedics and Related Research, no. 262, pp. 3-11, 1991.
16. K. Zimmermann, A. Haas, and A. Oxenius, "Systemic antibody responses to gut microbes in health and disease, " Gut Microbes, vol. 3, no. 1, pp. 42-47, 2012.
17. J. Karbach, A. Neumann, K. Brand, et al., "Phase I clinical trial of mixed bacterial vaccine (Coleys toxins) in patients with NYESO expressing cancers: immunological effects and clinical activity, " Clinical Cancer Research, vol. 18, no. 19, pp. 5449-5459, 2012.
18. J. M. Park and D. E. Fisher, "Testimony from the bedside: from Coleys toxins to targeted immunotherapy, " Cancer Cell, vol. 18, no. 1, pp. 9-10, 2010.
19. I. Gresser, "A. Chekhov, M. D., and Coleys toxins, " The New England Journal of Medicine, vol. 317, no. 7, p. 457, 1987.
20. A. Pinto, S. Morello, and R. Sorrentino, "Lung cancer and tolllike receptors, " Cancer Immunology, Immunotherapy, vol. 60, no. 9, pp. 1211-1220, 2011.
21. S. Rakoff-Nahoum and R. Medzhitov, "Toll-like receptors and cancer, " Nature Reviews Cancer, vol. 9, no. 1, pp. 57-63, 2009.
22. R. F. Wang, Y. Miyahara, and H. Y. Wang, "Toll-like receptors and immune regulation: implications for cancer therapy, " Oncogene, vol. 27, no. 2, pp. 181-189, 2008.
23. M. A. J. Hullar, A. N. Burnett-Hartman, and J. W. Lampe, "Gut microbes, diet, and cancer, " Cancer Treatment and Research, vol. 159, pp. 377-399, 2014.
24. I. E. Mulder, B. Schmidt, C. R. Stokes, et al., "Environmentallyacquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces, " BMC Biology, vol. 7, article 79, 2009.
25. J. E. Koenig, A. Spor, N. Scalfone, et al., "Succession of microbial consortia in the developing infant gut microbiome, " Proceedings of the National Academy of Sciences of the United States of America, vol. 108, supplement 1, pp. 4578-4585, 2011.
26. C. de Filippo, D. Cavalieri, M. di Paola, et al., "Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa, " Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 33, pp. 14691-14696, 2010.
27. R. Jumpertz, D. S. Le, P. J. Turnbaugh, et al., "Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans, " The American Journal of Clinical Nutrition, vol. 94, no. 1, pp. 58-65, 2011.
28. L. Dethlefsen and D. A. Relman, "Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation, " Proceedings of the National Academy of Sciences of the United States of America, vol. 108, supplement 1, pp. 4554-4561, 2011.
29. P. D. Cotter, C. Stanton, R. P. Ross, and C. Hill, "The impact of antibiotics on the gut microbiota as revealed by high throughput DNA sequencing, " Discovery Medicine, vol. 13, no. 70, pp. 193-199, 2012.
30. H.-J. Wu, I. I. Ivanov, J. Darce, et al., "Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells, " Immunity, vol. 32, no. 6, pp. 815-827, 2010.
31. M. Blaser, "Antibiotic overuse: stop the killing of beneficial bacteria, " Nature, vol. 476, no. 7361, pp. 393-394, 2011.
32. J. Hansson, N. Bosco, L. Favre, et al., "Influence of gut microbiota on mouse B2 B cell ontogeny and function, " Molecular Immunology, vol. 48, no. 9-10, pp. 1091-1101, 2011.
33. K. Suzuki, B. Meek, Y. Doi, et al., "Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 7, pp. 1981-1986, 2004.
34. O. Takeuchi and S. Akira, "Pattern recognition receptors and inflammation, " Cell, vol. 140, no. 6, pp. 805-820, 2010.
35. S. Akira, S. Uematsu, and O. Takeuchi, "Pathogen recognition and innate immunity, " Cell, vol. 124, no. 4, pp. 783-801, 2006.
36. S. Akira and K. Takeda, "Toll-like receptor signalling, " Nature Reviews Immunology, vol. 4, no. 7, pp. 499-511, 2004.
37. G. Trinchieri and A. Sher, "Cooperation of Toll-like receptor signals in innate immune defence, " Nature Reviews Immunology, vol. 7, no. 3, pp. 179-190, 2007.
38. C. Trumpfheller, M. Caskey, G. Nchinda, et al., "The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine, " Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 7, pp. 2574-2579, 2008.
39. M. L. Salem, A. N. Kadima, D. J. Cole, and W. E. Gilland ers, "Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity, " Journal of Immunotherapy, vol. 28, no. 3, pp. 220-228, 2005.
40. H. Navabi, B. Jasani, A. Reece, et al., "A clinical grade poly I:Canalogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro, " Vaccine, vol. 27, no. 1, pp. 107-115, 2009.
41. A. Poltorak, P. Ricciardi-Castagnoli, S. Citterio, and B. Beutler, "Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation, " Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 5, pp. 2163-2167, 2000.
42. M. R. Chicoine, M. Zahner, E. K. Won, et al., "The in vivo antitumoral effects of lipopolysaccharide against glioblastoma multiforme are mediated in part by toll-like receptor 4, " Neurosurgery, vol. 60, no. 2, pp. 372-381, 2007.
43. P. W. Chen, M. Wang, V. Bronte, Y. Zhai, S. A. Rosenberg, and N. P. Restifo, "Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumorassociated antigen, " Journal of Immunology, vol. 156, no. 1, pp. 224-231, 1996.
44. M. B. Davis, D. Vasquez-Dunddel, J. Fu, E. Albesiano, D. Pardoll, and Y. J. Kim, "Intratumoral administration of TLR4 agonist absorbed into a cellular vector improves antitumor responses, " Clinical Cancer Research, vol. 17, no. 12, pp. 3984-3992, 2011.
45. L. Shapira, W. A. Soskolne, Y. Houri, V. Barak, A. Halabi, and A. Stabholz, "Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion, " Infection and Immunity, vol. 64, no. 3, pp. 825-828, 1996.
46. H. Okamoto, S. Shoin, S. Koshimura, and R. Shimizu, "Studies on the anticancer and streptolysin S-forming abilities of hemolytic streptococci., " Japanese Journal of Microbiology, vol. 11, no. 4, pp. 323-326, 1967.
47. M. Okamoto, T. Oshikawa, T. Tano, et al., "Mechanism of anticancer host response induced by OK-432, a streptococcal preparation, mediated by phagocytosis and Toll-like receptor 4 signaling, "The Journal of Immunotherapy, vol. 29, no. 1, pp. 78-86, 2006.
48. L. G. Burdelya, A. S. Gleiberman, I. Toshkov, et al., "Tolllike receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and neck cancer radiotherapy, " International Journal of Radiation Oncology, Biology, Physics, vol. 83, no. 1, pp. 228-234, 2012.
49. L. G. Burdelya, V. I. Krivokrysenko, T. C. Tallant, et al., "An agonist of toll-like receptor 5 has radioprotective activity in mouse and primatemodels, " Science, vol. 320, no. 5873, pp. 226-230, 2008.
50. S. S. Diebold, T. Kaisho, H. Hemmi, S. Akira, and C. Reis E Sousa, "Innate antiviral responses by means of TLR7-mediated recognition of single-strand ed RNA, " Science, vol. 303, no. 5663, pp. 1529-1531, 2004.
51. F. Heil, H. Hemmi, H. Hochrein, et al., "Species-specific recognition of single-strand ed RNA via toll-like receptor 7 and 8, " Science, vol. 303, no. 5663, pp. 1526-1529, 2004.
52. J. M. Lund, L. Alexopoulou, A. Sato, et al., "Recognition of single-strand ed RNA viruses by Toll-like receptor 7, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 15, pp. 5598-5603, 2004.
53. C. Manegold, N. van Zand wijk, A. Szczesna, et al., "A phase III rand omized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer, " Annals of Oncology, vol. 23, no. 1, pp. 72-77, 2012.
54. M. R. Weihrauch, S. Arisen, E. Jurkiewicz, et al., "Phase I/II combined chemoimmunotherapy with carcinoembryonic antigenderived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer, " Clinical Cancer Research, vol. 11, no. 16, pp. 5993-6001, 2005.
55. V. Hornung, S. Rothenfusser, S. Britsch, et al., "Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides, " The Journal of Immunology, vol. 168, no. 9, pp. 4531-4537, 2002.
56. K. Schwarz, T. Storni, V. Manolova, et al., "Role of toll-like receptors in costimulating cytotoxic T cell responses, " European Journal of Immunology, vol. 33, no. 6, pp. 1465-1470, 2003.
57. S. K. Datta, V. Redecke, K. R. Prilliman, et al., "A subset of toll-like receptor ligand s induces cross-presentation by bone marrow-derived dendritic cells, " Journal of Immunology, vol. 170, no. 8, pp. 4102-4110, 2003.
58. U. Wille-Reece, B. J. Flynn, K. Lore, et al., "HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates, " Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 42, pp. 15190-15194, 2005.
59. M. Kwissa, R. R. Amara, H. L. Robinson, et al., "Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus, " The Journal of Experimental Medicine, vol. 204, no. 11, pp. 2733-2746, 2007.
60. I. Caramalho, T. Lopes-Carvalho, D. Ostler, S. Zelenay, M. Haury, and J. Demengeot, "Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide, " Journal of Experimental Medicine, vol. 197, no. 4, pp. 403-411, 2003.
61. G. Peng, Z. Guo, Y. Kiniwa, et al., "Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function, " Science, vol. 309, no. 5739, pp. 1380-1384, 2005.
62. R. P. M. Sutmuller, M. H. M. G. M. den Brok, M. Kramer, et al., "Toll-like receptor 2 controls expansion and function of regulatory T cells, "The Journal of Clinical Investigation, vol. 116, no. 2, pp. 485-494, 2006.
63. B. Huang, J. Zhao, J. C. Unkeless, Z. H. Feng, and H. Xiong, "TLR signaling by tumor and immune cells: a double-edged sword, " Oncogene, vol. 27, no. 2, pp. 218-224, 2008.
64. D. Hanahan and R. A. Weinberg, "Hallmarks of cancer: the next generation, " Cell, vol. 144, no. 5, pp. 646-674, 2011.
65. S. Kaczanowska, A. M. Joseph, and E. Davila, "TLR agonists: our best frenemy in cancer immunotherapy, " Journal of Leukocyte Biology, vol. 93, no. 6, pp. 847-863, 2013.
66. C. A. Klebanoff, N. Acquavella, Z. Yu, and N. P. Restifo, "Therapeutic cancer vaccines: are we there yet?" Immunological Reviews, vol. 239, no. 1, pp. 27-44, 2011.
67. S. A. Rosenberg, J. C. Yang, and N. P. Restifo, "Cancer immunotherapy: moving beyond current vaccines, " Nature Medicine, vol. 10, no. 9, pp. 909-915, 2004.
68. A. P. Bally, P. Lu, Y. Tang, et al., "NF-κB regulates PD-1 expression in macrophages, " The Journal of Immunology, vol. 194, no. 9, pp. 4545-4554, 2015.
69. S. A. Rosenberg and N. P. Restifo, "Adoptive cell transfer as personalized immunotherapy for human cancer, " Science, vol. 348, no. 6230, pp. 62-68, 2015.
70. T. Baba, M. Sato-Matsushita, A. Kanamoto, et al., "Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A2402, " Journal of Translational Medicine, vol. 8, article 84, 2010.
71. S. A. Rosenberg, J. C. Yang, D. J. Schwartzentruber, et al., "Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma, " Nature Medicine, vol. 4, no. 3, pp. 321-327, 1998.
72. D. J. Schwartzentruber, D. H. Lawson, J. M. Richards, et al., "gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma, "TheNewEngland Journal ofMedicine, vol. 364, no. 22, pp. 2119-2127, 2011.
73. Y. Hailemichael, Z. Dai, N. Jaffarzad, et al., "Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletion, " Nature Medicine, vol. 19, no. 4, pp. 465-472, 2013.
74. D. E. Speiser, D. Lienard, N. Rufer, et al., "Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909, " Journal of Clinical Investigation, vol. 115, no. 3, pp. 739-746, 2005.
75. C. M. Paulos and C. H. June, "Putting the brakes on BTLA in T cell-mediated cancer immunotherapy, " Journal of Clinical Investigation, vol. 120, no. 1, pp. 76-80, 2010.
76. L. Derre, J.-P. Rivals, C. Jand us, et al., "BTLAmediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination, " The Journal of Clinical Investigation, vol. 120, no. 1, pp. 157-167, 2010.
77. S. A. Rosenberg, "Progress in human tumour immunology and immunotherapy, " Nature, vol. 411, no. 6835, pp. 380-384, 2001.
78. M. E. Dudley, J. C. Yang, R. Sherry, et al., "Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens, " Journal of Clinical Oncology, vol. 26, no. 32, pp. 5233-5239, 2008.
79. M. J. Besser, R. Shapira-Frommer, A. J. Treves, et al., "Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients, " Journal of Immunotherapy, vol. 32, no. 4, pp. 415-423, 2009.
80. S. A. Rosenberg and M. E. Dudley, "Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, supplement 2, pp. 14639-14645, 2004.
81. S. A. Rosenberg, B. S. Packard, P. M. Aebersold, et al., "Use of tumor-infiltrating lymphocyts and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report, "The New England Journal of Medicine, vol. 319, no. 25, pp. 1676-1680, 1988.
82. M. A. de Witte, M. Coccoris, M. C. Wolkers, et al., "Targeting self-antigens through allogeneic TCR gene transfer, " Blood, vol. 108, no. 3, pp. 870-877, 2006.
83. P. D. Greenberg, D. E. Kern, and M. A. Cheever, "Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+, 2-T cells. Tumor eradication does not require participation of cytotoxic T cells, " The Journal of Experimental Medicine, vol. 161, no. 5, pp. 1122-1134, 1985.
84. D. R. Surman, M. E. Dudley, W. W. Overwijk, and N. P. Restifo, "Cutting edge: CD4+ T cell control of CD8+ T cell reactivity to a model tumor antigen, " Journal of Immunology, vol. 164, no. 2, pp. 562-565, 2000.
85. C. E. Touloukian, W. W. Leitner, S. L. Topalian, et al., "Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice, " The Journal of Immunology, vol. 164, no. 7, pp. 3535-3542, 2000.
86. L. Gattinoni, C. A. Klebanoff, D. C. Palmer, et al., "Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells, " The Journal of Clinical Investigation, vol. 115, no. 6, pp. 1616-1626, 2005.
87. C. A. Klebanoff, L. Gattinoni, and N. P. Restifo, "CD8+ Tcell memory in tumor immunology and immunotherapy, " Immunological Reviews, vol. 211, pp. 214-224, 2006.
88. C. S. Hinrichs, L. Gattinoni, and N. P. Restifo, "Programming CD8+ T cells for effective immunotherapy, " Current Opinion in Immunology, vol. 18, no. 3, pp. 363-370, 2006.
89. M. E. Dudley, J. R. Wunderlich, P. F. Robbins, et al., "Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes, " Science, vol. 298, no. 5594, pp. 850-854, 2002.
90. L. N. Hwang, Z. Yu, D. C. Palmer, and N. P. Restifo, "The in vivo expansion rate of properly stimulated transferred CD8+ T cells exceeds that of an aggressively growing mouse tumor, " Cancer Research, vol. 66, no. 2, pp. 1132-1138, 2006.
91. D. C. Palmer, S. Balasubramaniam, K.-I. Hanada, et al., "Vaccine-stimulated, adoptively transferred CD8+ T cells traffic indiscriminately and ubiquitously while mediating specific tumor destruction, " Journal of Immunology, vol. 173, no. 12, pp. 7209-7216, 2004.
92. D. L. Porter, B. L. Levine, M. Kalos, A. Bagg, and C. H. June, "Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia, "The New England Journal of Medicine, vol. 365, no. 8, pp. 725-733, 2011.
93. S. A. Grupp, M. Kalos, D. Barrett, et al., "Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, " The New England Journal ofMedicine, vol. 368, no. 16, pp. 1509-1518, 2013.
94. V. T. DeVita Jr. and E. Chu, "A history of cancer chemotherapy, " Cancer Research, vol. 68, no. 21, pp. 8643-8653, 2008.
95. C. Wrzesinski, C. M. Paulos, L. Gattinoni, et al., "Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8+ T cells, " The Journal of Clinical Investigation, vol. 117, no. 2, pp. 492-501, 2007.
96. P. Muranski, A. Boni, C. Wrzesinski, et al., "Increased intensity lymphodepletion and adoptive immunotherapy-how far can we go?"Nature Clinical PracticeOncology, vol. 3, no. 12, pp. 668-681, 2006.
97. C. Wrzesinski and N. P. Restifo, "Less ismore: lymphodepletion followed by hematopoietic stemcell transplant augments adoptive T-cell-based anti-tumor immunotherapy, " Current Opinion in Immunology, vol. 17, no. 2, pp. 195-201, 2005.
98. A. Fefer, "Immunotherapy and chemotherapy of Moloney sarcoma virus-induced tumors in mice, " Cancer Research, vol. 29, no. 12, pp. 2177-2183, 1969.
99. I. Hellstrom, K. E. Hellstrom, G. E. Pierce, and A. Fefer, "Studies onimmunity to autochthonousmouse tumors, " Transplantation Proceedings, vol. 1, no. 1, pp. 90-94, 1969.
100. M. A. Cheever, P. D. Greenberg, and A. Fefer, "Specificity of adoptive chemoimmunotherapy of established syngeneic tumors, " Journal of Immunology, vol. 125, no. 2, pp. 711-714, 1980.
101. M. J. Berendt and R. J. North, "T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor, "The Journal of Experimental Medicine, vol. 151, no. 1, pp. 69-80, 1980.
102. W. Dummer, A. G. Niethammer, R. Baccala, et al., "T cell homeostatic proliferation elicits effective antitumor autoimmunity, " The Journal of Clinical Investigation, vol. 110, no. 2, pp. 185-192, 2002.
103. L. Gattinoni, D. J. Powell Jr., S. A. Rosenberg, and N. P. Restifo, "Adoptive immunotherapy for cancer: building on success, " Nature Reviews Immunology, vol. 6, no. 5, pp. 383-393, 2006.
104. J. F. Jacobs, S. Nierkens, C. G. Figdor, I. J. M. de Vries, and G. J. Adema, "Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy?" The Lancet Oncology, vol. 13, no. 1, pp. e32-e42, 2012.
105. Y. Kiniwa, Y. Miyahara, H. Y. Wang, et al., "CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer, " Clinical Cancer Research, vol. 13, no. 23, pp. 6947-6958, 2007.
106. P. B. Olkhanud, B. Damdinsuren, M. Bodogai, et al., "Tumorevoked regulatory B cells promote breast cancer metastasis by converting resting CD4+ T cells to T-regulatory cells, " Cancer Research, vol. 71, no. 10, pp. 3505-3515, 2011.
107. K. N. Kodumudi, A. Weber, A. A. Sarnaik, and S. Pilon-Thomas, "Blockade of myeloid-derived suppressor cells after induction of lymphopenia improves adoptive T cell therapy in a murine model of melanoma, " The Journal of Immunology, vol. 189, no. 11, pp. 5147-5154, 2012.
108. L. A. Geiselhart, C. A. Humphries, T. A. Gregorio, S. Mou, J. Subleski, and K. L. Komschlies, "IL-7 administration alters the CD4:CD8 ratio, increases T cell numbers, and increases T cell function in the absence of activation, " The Journal of Immunology, vol. 166, no. 5, pp. 3019-3027, 2001.
109. C. A. Klebanoff, S. E. Finkelstein, D. R. Surman, et al., "IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T Cells, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 7, pp. 1969-1974, 2004.
110. K. L. Komschlies, T. A. Gregorio, M. E. Gruys, T. C. Back, C. R. Faltynek, and R. H. Wiltrout, "Administration of recombinant human IL-7 to mice alters the composition of B-lineage cells and T cell subsets, enhances T cell function, and induces regression of established metastases, " The Journal of Immunology, vol. 152, no. 12, pp. 5776-5784, 1994.
111. A. Moroz, C. Eppolito, Q. Li, J. Tao, C. H. Clegg, and P. A. Shrikant, "IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21, " Journal of Immunology, vol. 173, no. 2, pp. 900-909, 2004.
112. E. A. Reits, J. W. Hodge, C. A. Herberts, et al., "Radiation modulates the peptide repertoire, enhancesMHC class I expression, and induces successful antitumor immunotherapy, " The Journal of Experimental Medicine, vol. 203, no. 5, pp. 1259-1271, 2006.
113. L. Gattinoni, S. E. Finkelstein, C. A. Klebanoff, et al., "Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells, " The Journal of Experimental Medicine, vol. 202, no. 7, pp. 907-912, 2005.
114. K. E. Hellstrom, I. Hellstrom, J. A. Kant, and J. D. Tamerius, "Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population, " Journal of Experimental Medicine, vol. 148, no. 3, pp. 799-804, 1978.
115. A. Shigematsu, Y. Adachi, N. Koike-Kiriyama, et al., "Effects of low-dose irradiation on enhancement of immunity by dendritic cells, " Journal of Radiation Research, vol. 48, no. 1, pp. 51-55, 2007.
116. C. Q. Xun, J. S. Thompson, C. D. Jennings, S. A. Brown, and M. B. Widmer, "Effect of total body irradiation, busulfancyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice, " Blood, vol. 83, no. 8, pp. 2360-2367, 1994.
117. J. S. Bowers, M. H. Nelson, S. Kundimi, et al., "Dendritic cells in irradiated mice trigger the functional plasticity and antitumor activity of adoptively transferred Tc17 cells via IL-12 signaling, " Clinical Cancer Research, 2015.
118. J. Huang, Q. J. Wang, S. Yang, et al., "Irradiationenhanceshuman T-cell function by upregulating CD70 expression on antigenpresenting cells in vitro, " Journal of Immunotherapy, vol. 34, no. 4, pp. 327-335, 2011.
119. H. Torihata, F. Ishikawa, Y. Okada, et al., "Irradiation upregulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells, " Immunology, vol. 112, no. 2, pp. 219-227, 2004.
120. S. Z. Liu, S. Z. Jin, X. D. Liu, and Y. M. Sun, "Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiationinduced immune changes., " BMC Immunology, vol. 2, article 8, 2001.
121. Y. H. Kim, M. Duvic, E. Obitz, et al., "Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma, " Blood, vol. 109, no. 11, pp. 4655-4662, 2007.
122. P. Attia, D. J. Powell Jr., A. V. Maker, R. J. Kreitman, I. Pastan, and S. A. Rosenberg, "Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2, " Journal of Immunotherapy, vol. 29, no. 2, pp. 208-214, 2006.
123. D. J. Powell Jr., C. R. De Vries, T. Allen, M. Ahmadzadeh, and S. A. Rosenberg, "Inability to mediate prolonged reduction of regulatory T cells after transfer of autologous CD25-depleted PBMC and interleukin-2 after lymphodepleting chemotherapy, " Journal of Immunotherapy, vol. 30, no. 4, pp. 438-447, 2007.
124. P. McLaughlin, A. J. Grillo-Lopez, B. K. Link, et al., "Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program, " Journal of Clinical Oncology, vol. 16, no. 8, pp. 2825-2833, 1998.
125. D. G. Maloney, A. J. Grillo-Lopez, C. A. White, et al., "IDECC2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkins lymphoma, " Blood, vol. 90, no. 6, pp. 2188-2195, 1997.
126. J. N. Kochenderfer, M. E. Dudley, S. A. Feldman, et al., "B-cell depletion and remissions of malignancy along with cytokineassociated toxicity in a clinical trial of anti-CD19 chimericantigen-receptor-transduced T cells, " Blood, vol. 119, no. 12, pp. 2709-2720, 2012.
127. J. N. Kochenderfer, Z. Yu, D. Frasheri, N. P. Restifo, and S. A. Rosenberg, "Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells, " Blood, vol. 116, no. 19, pp. 3875-3886, 2010.
128. O. Boyman, M. Kovar, M. P. Rubinstein, C. D. Surh, and J. Sprent, "Selective stimulation of T cell subsets with antibodycytokine immune complexes, " Science, vol. 311, no. 5769, pp. 1924-1927, 2006.
129. M. P. Rubinstein, M. Kovar, J. F. Purton, et al., "Converting IL-15 to a superagonist by binding to soluble IL-15R, " Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 24, pp. 9166-9171, 2006.
130. D. J. Cole and M. P. Rubinstein, "Soluble IL-15/IL-15R complexes in human serum, " Blood, vol. 120, no. 1, pp. 1-2, 2012.
131. H.-I. Cho, E. Reyes-Vargas, J. C. Delgado, and E. Celis, "A potent vaccination strategy that circumvents lymphodepletion for effective antitumor adoptive T-cell therapy, " Cancer Research, vol. 72, no. 8, pp. 1986-1995, 2012.
132. G. L. Beatty, E. G. Chiorean, M. P. Fishman, et al., "CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans, " Science, vol. 331, no. 6024, pp. 1612-1616, 2011.
133. C. Carpenito, M. C. Milone, R. Hassan, et al., "Control of large, established tumor xenograftswith genetically retargeted human T cells containingCD28 and CD137 domains, " Proceedings of the NationalAcademy of Sciences of theUnited States ofAmerica, vol. 106, no. 9, pp. 3360-3365, 2009.
134. J. R. Brahmer, S. S. Tykodi, L. Q. M. Chow, et al., "Safety and activity of anti-PD-L1 antibody in patients with advanced cancer, "The New England Journal of Medicine, vol. 366, no. 26, pp. 2455-2465, 2012.
135. F. S. Hodi, S. J. ODay, D. F. McDermott, et al., "Improved survival with ipilimumab in patients with metastatic melanoma, " The New England Journal of Medicine, vol. 363, no. 8, pp. 711-723, 2010.
136. M. Kalos, B. L. Levine, D. L. Porter, et al., "T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia, " Science TranslationalMedicine, vol. 3, no. 95, Article ID95ra73, 2011.
137. P. Muranski, Z. A. Borman, S. P. Kerkar, et al., "Th17 cells are long lived and retain a stemcell-like molecular signature, " Immunity, vol. 35, no. 6, pp. 972-985, 2011.
138. S. Wei, E. Zhao, I. Kryczek, and W. Zou, "Th17 cells have stem cell-like features and promote long-term immunity, " OncoImmunology, vol. 1, no. 4, pp. 516-519, 2012.
139. A. Dzutsev, R. S. Goldszmid, S. Viaud, L. Zitvogel, and G. Trinchieri, "The role of the microbiota in inflammation, carcinogenesis, and cancer therapy, " European Journal of Immunology, vol. 45, no. 1, pp. 17-31, 2015.
140. S. Viaud, R. Daillere, I. G. Boneca, et al., "Gut microbiome and anticancer immune response: really hot Sh∗t!, " Cell Death & Differentiation, vol. 22, pp. 199-214, 2015.
141. N. Iida, A. Dzutsev, C. A. Stewart, et al., "Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment, " Science, vol. 342, no. 6161, pp. 967-970, 2013.
142. S. Viaud, F. Saccheri, G. Mignot, et al., "The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide, " Science, vol. 342, no. 6161, pp. 971-976, 2013.
143. M. Veldhoen, R. J. Hocking, C. J. Atkins, R. M. Locksley, and B. Stockinger, "TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells, " Immunity, vol. 24, no. 2, pp. 179-189, 2006.
144. I. I. Ivanov, R. D. L. Frutos, N. Manel, et al., "Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine, " Cell Host and Microbe, vol. 4, no. 4, pp. 337-349, 2008.
145. I. I. Ivanov, K. Atarashi, N. Manel, et al., "Induction of intestinal Th17 cells by segmented filamentous bacteria, " Cell, vol. 139, no. 3, pp. 485-498, 2009.
146. M. A. Kriegel, E. Sefik, J. A. Hill, H.-J. Wu, C. Benoist, and D. Mathis, "Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice, " Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 28, pp. 11548-11553, 2011.
147. C. M. Paulos, C. Wrzesinski, A. Kaiser, et al., "Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling, " The Journal of Clinical Investigation, vol. 117, no. 8, pp. 2197-2204, 2007.
148. M. H. Nelson, S. Kundimi, J. S. Bowers, et al., " The inducible costimulator augments Tc17 cell responses to self and tumor tissue, " The Journal of Immunology, vol. 194, no. 4, pp. 1737-1747, 2015.