Targeting tregs in malignant brain cancer: Overcoming IDO

Frontiers in Immunology

Volumn 4, Issue MAY, 2013, Pages

  Wainwright, Derek A ^a   Dey, Mahua ^a   Chang, Alan ^a   Lesniak, Maciej S ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

Glioblastoma multiforme; IDO (indoleamine 2,3 dioxygenase); Malignant glioma; Natural tregs; Regulatory T cells; Tregs; Tumor induced tregs

Indexed keywords

CD134 ANTIGEN; CD200 ANTIGEN; CYCLOPHOSPHAMIDE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACLIZUMAB; DENILEUKIN DIFTITOX; GAMMA INTERFERON; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; INDOLEAMINE 2, 3 DIOXYGENASE; INTERLEUKIN 2 RECEPTOR ALPHA; OX40 LIGAND; PROTEIN P21; PROTEIN P53; STAT3 PROTEIN; TEMOZOLOMIDE; TRANSCRIPTION FACTOR FOXP3; TRYPTOPHAN; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ANTIGEN SPECIFICITY; AUTOIMMUNITY; BLOOD BRAIN BARRIER; BRAIN CANCER; CARCINOGENESIS; CATABOLISM; CELL DIFFERENTIATION; CELL PROLIFERATION; CHEMOTAXIS; GLIOBLASTOMA; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; PROTEIN INTERACTION; REGULATORY T LYMPHOCYTE; REVIEW; TUMOR ASSOCIATED LEUKOCYTE; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

EID: 84883797338     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00116     Document Type: Review

References (168)

1. Adams, O., Besken, K., Oberdorfer, C., Mackenzie, C. R., Takikawa, O., and Daubener, W. (2004). Role of indoleamine-2,3-dioxygenase in alpha/beta and gamma interferon-mediated antiviral effects against herpes simplex virus infections. J. Virol. 78, 2632-2636.
2. Agarwalla, P., Barnard, Z., Fecci, P., Dranoff, G., and Curry, W. T. Jr. (2012). Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors. J. Immunother. 35, 385-389.
3. Allan, S. E., Passerini, L., Bacchetta, R., Crellin, N., Dai, M., Orban, P. C., et al. (2005). The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 115, 3276-3284.
4. Ansell, S. M., Tang, H., Kurtin, P. J., Koenig, P. A., Nowakowski, G. S., Nikcevich, D. A., et al. (2012). Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma. Leukemia 26, 1046-1052.
5. Attia, P., Maker, A. V., Haworth, L. R., Rogers-Freezer, L., and Rosenberg, S. A. (2005a). Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J. Immunother. 28, 582-592.
6. Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., et al. (2005b). Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J. Clin. Oncol. 23, 6043-6053.
7. Banissi, C., Ghiringhelli, F., Chen, L., and Carpentier, A. F. (2009). Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model. Cancer Immunol. Immunother. 58, 1627-1634.
8. Basu, G. D., Tinder, T. L., Bradley, J. M., Tu, T., Hattrup, C. L., Pockaj, B. A., et al. (2006). Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO. J. Immunol. 177, 2391-2402.
9. Bennett, C. L., Christie, J., Ramsdell, F., Brunkow, M. E., Ferguson, P. J., Whitesell, L., et al. (2001). The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20-21.
10. Berd, D., Maguire, H. C. Jr., Mccue, P., and Mastrangelo, M. J. (1990). Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J. Clin. Oncol. 8, 1858-1867.
11. Bilate, A. M., and Lafaille, J. J. (2012). Induced CD4+FOXP3+ regulatory T cells in immune tolerance. Annu. Rev. Immunol. 30, 733-758.
12. Bill, M. A., Fuchs, J. R., Li, C., Yui, J., Bakan, C., Benson, D. M. Jr., et al. (2010). The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol. Cancer 9, 165.
13. Blatner, N. R., Mulcahy, M. F., Dennis, K. L., Scholtens, D., Bentrem, D. J., Phillips, J. D., et al. (2012). Expression of RORgammat marks a pathogenic regulatory T cell subset in human colon cancer. Sci. Transl. Med. 4, 164ra159.
14. Bot, I., Blank, C. U., Boogerd, W., and Brandsma, D. (2013). Neurological immune-related adverse events of ipilimumab. Pract. Neurol. PMID:23487828. [Epub ahead of print].
15. Braun, D., Longman, R. S., and Albert, M. L. (2005). A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood 106, 2375-2381.
16. Burke, F., Knowles, R. G., East, N., and Balkwill, F. R. (1995). The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human interferon-gamma in vivo. Int. J. Cancer 60, 115-122.
17. Burton, J. H., Mitchell, L., Thamm, D. H., Dow, S. W., and Biller, B. J. (2011). Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits angiogenesis in dogs with soft tissue sarcoma. J. Vet. Intern. Med. 25, 920-926.
18. Carlin, J. M., Borden, E. C., Sondel, P. M., and Byrne, G. I. (1987). Biologic-response-modifier-induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J. Immunol. 139, 2414-2418.
19. Carlin, J. M., Borden, E. C., Sondel, P. M., and Byrne, G. I. (1989). Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J. Leukoc. Biol. 45, 29-34.
20. Casares, N., Rudilla, F., Arribillaga, L., Llopiz, D., Riezu-Boj, J. I., Lozano, T., et al. (2010). A peptide inhibitor of FOXP3 impairs regulatory T cell activity and improves vaccine efficacy in mice. J. Immunol. 185, 5150-5159.
21. Chow, L. M., Endersby, R., Zhu, X., Rankin, S., Qu, C., Zhang, J., et al. (2011). Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain. Cancer Cell 19, 305-316.
22. Cohen, A. D., Schaer, D. A., Liu, C., Li, Y., Hirschhorn-Cymmerman, D., Kim, S. C., et al. (2010). Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS ONE 5:e10436. doi:10.1371/journal.pone.0010436
23. Crane, C. A., Ahn, B. J., Han, S. J., and Parsa, A. T. (2012). Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory T cells: implications for immunotherapy. Neuro-oncology 14, 584-595.
24. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942-949.
25. Curotto de Lafaille, M. A., and Lafaille, J. J. (2009). Natural and adaptive FOXP3+ regulatory T cells: more of the same or a division of labor? Immunity 30, 626-635.
26. Curtin, J. F., Candolfi, M., Fakhouri, T. M., Liu, C., Alden, A., Edwards, M., et al. (2008). Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials. PLoS ONE 3:e1983. doi:10.1371/journal.pone.0001983
27. Dannull, J., Su, Z., Rizzieri, D., Yang, B. K., Coleman, D., Yancey, D., et al. (2005). Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 115, 3623-3633.
28. Davies, M. N., Bayry, J., Tchilian, E. Z., Vani, J., Shaila, M. S., Forbes, E. K., et al. (2009). Toward the discovery of vaccine adjuvants: coupling in silico screening and in vitro analysis of antagonist binding to human and mouse CCR4 receptors. PLoS ONE 4:e8084. doi:10.1371/journal.pone.0008084
29. deLeeuw, R. J., Kost, S. E., Kakal, J. A., and Nelson, B. H. (2012). The prognostic value of FOXP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. Clin. Cancer Res. 18, 3022-3029.
30. El Andaloussi, A., Han, Y., and Lesniak, M. S. (2006). Prolongation of survival following depletion of CD4+CD25+ regulatory T cells in mice with experimental brain tumors. J. Neurosurg. 105, 430-437.
31. El Andaloussi, A., and Lesniak, M. S. (2006). An increase in CD4+CD25+Foxp3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme. Neuro-oncology 8, 234-243.
32. El Andaloussi, A., and Lesniak, M. S. (2007). CD4+ CD25+ FOXP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas. J. Neurooncol. 83, 145-152.
33. Fallarino, F., Asselin-Paturel, C., Vacca, C., Bianchi, R., Gizzi, S., Fioretti, M. C., et al. (2004). Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J. Immunol. 173, 3748-3754.
34. Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., et al. (2003). Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol. 4, 1206-1212.
35. Fecci, P. E., Mitchell, D. A., Whitesides, J. F., Xie, W., Friedman, A. H., Archer, G. E., et al. (2006a). Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 66, 3294-3302.
36. Fecci, P. E., Sweeney, A. E., Grossi, P. M., Nair, S. K., Learn, C. A., Mitchell, D. A., et al. (2006b). Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells. Clin. Cancer Res. 12, 4294-4305.
37. Fecci, P. E., Ochiai, H., Mitchell, D. A., Grossi, P. M., Sweeney, A. E., Archer, G. E., et al. (2007). Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function. Clin. Cancer Res. 13, 2158-2167.
38. Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J., et al. (2007). Epigenetic control of the FOXP3 locus in regulatory T cells. PLoS Biol. 5:e38. doi:10.1371/journal.pbio.0050038
39. Fong, B., Jin, R., Wang, X., Safaee, M., Lisiero, D. N., Yang, I., et al. (2012). Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. PLoS ONE 7:e32614. doi:10.1371/journal.pone.0032614
40. Fontenot, J. D., Gavin, M. A., and Rudensky, A. Y. (2003). FOXP3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330-336.
41. Friberg, M., Jennings, R., Alsarraj, M., Dessureault, S., Cantor, A., Extermann, M., et al. (2002). Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int. J. Cancer 101, 151-155.
42. Fujigaki, H., Saito, K., Lin, F., Fujigaki, S., Takahashi, K., Martin, B. M., et al. (2006). Nitration and inactivation of IDO by peroxynitrite. J. Immunol. 176, 372-379.
43. Ge, Y., Domschke, C., Stoiber, N., Schott, S., Heil, J., Rom, J., et al. (2012). Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol. Immunother. 61, 353-362.
44. Germain, R. N. (2002). T-cell development and the CD4-CD8 lineage decision. Nat. Rev. Immunol. 2, 309-322.
45. Gounaris, E., Blatner, N. R., Dennis, K., Magnusson, F., Gurish, M. F., Strom, T. B., et al. (2009). T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res. 69, 5490-5497.
46. Grant, R., and Kapoor, V. (2003). Inhibition of indoleamine 2,3-dioxygenase activity in IFN-gamma stimulated astroglioma cells decreases intracellular NAD levels. Biochem. Pharmacol. 66, 1033-1036.
47. Grant, R. S., Naif, H., Espinosa, M., and Kapoor, V. (2000). IDO induction in IFN-gamma activated astroglia: a role in improving cell viability during oxidative stress. Redox Rep. 5, 101-104.
48. Grauer, O. M., Nierkens, S., Bennink, E., Toonen, L. W., Boon, L., Wesseling, P., et al. (2007). CD4+FOXP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int. J. Cancer 121, 95-105.
49. Grauer, O. M., Sutmuller, R. P., Van Maren, W., Jacobs, J. F., Bennink, E., Toonen, L. W., et al. (2008). Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model. Int. J. Cancer 122, 1794-1802.
50. Grohmann, U., Fallarino, F., Bianchi, R., Belladonna, M. L., Vacca, C., Orabona, C., et al. (2001). IL-6 inhibits the tolerogenic function of CD8 alpha+ dendritic cells expressing indoleamine 2,3-dioxygenase. J. Immunol. 167, 708-714.
51. Haribhai, D., Williams, J. B., Jia, S., Nickerson, D., Schmitt, E. G., Edwards, B., et al. (2011). A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 35, 109-122.
52. Hatiboglu, M. A., Kong, L. Y., Wei, J., Wang, Y., Mcenery, K. A., Fuller, G. N., et al. (2012). The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models. Int. J. Cancer 131, 8-17.
53. Hayaishi, O., Hirata, F., Fujiwara, M., Senoh, S., and Tokuyama, T. (1975). Indoleamine 2,3-dioxygenase. Note II. Biological function. Acta Vitaminol Enzymol 29, 291-293.
54. Hayaishi, O., and Yoshida, R. (1978). Specific induction of pulmonary indoleamine 2,3-dioxygenase by bacterial lipopolysaccharide. Ciba Found. Symp. 65, 199-203.
55. Heimberger, A. B., Abou-Ghazal, M., Reina-Ortiz, C., Yang, D. S., Sun, W., Qiao, W., et al. (2008a). Incidence and prognostic impact of FOXP3+ regulatory T cells in human gliomas. Clin. Cancer Res. 14, 5166-5172.
56. Heimberger, A. B., Sun, W., Hussain, S. F., Dey, M., Crutcher, L., Aldape, K., et al. (2008b). Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study. Neuro-oncology 10, 98-103.
57. Hindley, J. P., Ferreira, C., Jones, E., Lauder, S. N., Ladell, K., Wynn, K. K., et al. (2011). Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors. Cancer Res. 71, 736-746.
58. Hirata, F., Nomiyama, S., and Hayaishi, O. (1975). Indoleamine 2,3-dioxygenase. Note I. Catalytic and molecular properties. Acta Vitaminol. Enzymol. 29, 288-290.
59. Hirata, F., Ohnishi, T., and Hayaishi, O. (1977). Indoleamine 2,3-dioxygenase. Characterization and properties of enzyme. O2-complex. J. Biol. Chem. 252, 4637-4642.
60. Hirschhorn-Cymerman, D., Rizzuto, G. A., Merghoub, T., Cohen, A. D., Avogadri, F., Lesokhin, A. M., et al. (2009). OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis. J. Exp. Med. 206, 1103-1116.
61. Hori, S., Nomura, T., and Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor FOXP3. Science 299, 1057-1061.
62. Horwitz, D. A., Zheng, S. G., and Gray, J. D. (2008). Natural and TGF-beta-induced FOXP3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other. Trends Immunol. 29, 429-435.
63. Hotfilder, M., Knupfer, H., Mohlenkamp, G., Pennekamp, P., Knupfers, M., Van Gool, S., et al. (2000). Interferon-gamma increases IL-6 production in human glioblastoma cell lines. Anticancer Res. 20, 4445-4450.
64. Hou, D. Y., Muller, A. J., Sharma, M. D., Duhadaway, J., Banerjee, T., Johnson, M., et al. (2007). Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res. 67, 792-801.
65. Hsieh, C. S., Liang, Y., Tyznik, A. J., Self, S. G., Liggitt, D., and Rudensky, A. Y. (2004). Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 21, 267-277.
66. Hsieh, C. S., Zheng, Y., Liang, Y., Fontenot, J. D., and Rudensky, A. Y. (2006). An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7, 401-410.
67. Huijts, C. M., Santegoets, S. J., Van Den Eertwegh, A. J., Pijpers, L. S., Haanen, J. B., De Gruijl, T. D., et al. (2011). Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer. BMC Cancer 11:505. doi:10.1186/1471-2407-11-505
68. Hwu, P., Du, M. X., Lapointe, R., Do, M., Taylor, M. W., and Young, H. A. (2000). Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J. Immunol. 164, 3596-3599.
69. Jacobs, J. F., Idema, A. J., Bol, K. F., Grotenhuis, J. A., De Vries, I. J., Wesseling, P., et al. (2010). Prognostic significance and mechanism of Treg infiltration in human brain tumors. J. Neuroimmunol. 225, 195-199.
70. Jordan, J. T., Sun, W., Hussain, S. F., Deangulo, G., Prabhu, S. S., and Heimberger, A. B. (2008). Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunol. Immunother. 57, 123-131.
71. Josefowicz, S. Z., and Rudensky, A. (2009). Control of regulatory T cell lineage commitment and maintenance. Immunity 30, 616-625.
72. Kaminska, B., Kocyk, M., and Kijewska, M. (2013). TGF beta signaling and its role in glioma pathogenesis. Adv. Exp. Med. Biol. 986, 171-187.
73. Kim, T. G., Kim, C. H., Park, J. S., Park, S. D., Kim, C. K., Chung, D. S., et al. (2010). Immunological factors relating to the antitumor effect of temozolomide chemoimmunotherapy in a murine glioma model. Clin. Vaccine Immunol. 17, 143-153.
74. Kinjyo, I., Inoue, H., Hamano, S., Fukuyama, S., Yoshimura, T., Koga, K., et al. (2006). Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J. Exp. Med. 203, 1021-1031.
75. Kjaergaard, J., Tanaka, J., Kim, J. A., Rothchild, K., Weinberg, A., and Shu, S. (2000). Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res. 60, 5514-5521.
76. Kjaergaard, J., Wang, L. X., Kuriyama, H., Shu, S., and Plautz, G. E. (2005). Active immunotherapy for advanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines. J. Neurosurg. 103, 156-164.
77. Ko, K., Yamazaki, S., Nakamura, K., Nishioka, T., Hirota, K., Yamaguchi, T., et al. (2005). Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating FOXP3+CD25+CD4+ regulatory T cells. J. Exp. Med. 202, 885-891.
78. Kocher, M., Kunze, S., Eich, H. T., Semrau, R., and Muller, R. P. (2005). Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma. Strahlenther. Onkol. 181, 157-163.
79. Kong, L. Y., Wei, J., Sharma, A. K., Barr, J., Abou-Ghazal, M. K., Fokt, I., et al. (2009). A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells. Cancer Immunol. Immunother. 58, 1023-1032.
80. Kortylewski, M., Kujawski, M., Wang, T., Wei, S., Zhang, S., Pilon-Thomas, S., et al. (2005). Inhibiting STAT3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat. Med. 11, 1314-1321.
81. Kreitman, R. J., Wilson, W. H., White, J. D., Stetler-Stevenson, M., Jaffe, E. S., Giardina, S., et al. (2000). Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J. Clin. Oncol. 18, 1622-1636.
82. Langroudi, L., Hassan, Z. M., Ebtekar, M., Mahdavi, M., Pakravan, N., and Noori, S. (2010). A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model. Int. Immunopharmacol. 10, 1055-1061.
83. Lanzetta, G., Campanella, C., Rozzi, A., Nappa, M., Costa, A., Fedele, F., et al. (2003). Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Anticancer Res. 23, 5159-5164.
84. Liu, F., Cao, J., Wu, J., Sullivan, K., Shen, J., Ryu, B., et al. (2013). STAT3-Targeted Therapies Overcome the Acquired Resistance to Vemurafenib in Melanomas. J. Invest. Dermatol. doi:10.1038/jid.2013.32. [Epub ahead of print].
85. Liu, H., Xue, Z. T., Sjogren, H. O., Salford, L. G., and Widegren, B. (2007a). Low dose Zebularine treatment enhances immunogenicity of tumor cells. Cancer Lett. 257, 107-115.
86. Liu, V. C., Wong, L. Y., Jang, T., Shah, A. H., Park, I., Yang, X., et al. (2007b). Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J. Immunol. 178, 2883-2892.
87. Lob, S., Konigsrainer, A., Zieker, D., Brucher, B. L., Rammensee, H. G., Opelz, G., et al. (2009). IDO1 and IDO2 are expressed in human tumors: levo-but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol. Immunother. 58, 153-157.
88. Maes, W., Rosas, G. G., Verbinnen, B., Boon, L., De Vleeschouwer, S., Ceuppens, J. L., et al. (2009). DC vaccination with anti-CD25 treatment leads to long-term immunity against experimental glioma. Neuro-oncology 11, 529-542.
89. Mahnke, K., Schonfeld, K., Fondel, S., Ring, S., Karakhanova, S., Wiedemeyer, K., et al. (2007). Depletion of CD4+CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int. J. Cancer 120, 2723-2733.
90. Mailloux, A. W., and Young, M. R. (2010). Regulatory T-cell trafficking: from thymic development to tumor-induced immune suppression. Crit. Rev. Immunol. 30, 435-447.
91. Maker, A. V., Phan, G. Q., Attia, P., Yang, J. C., Sherry, R. M., Topalian, S. L., et al. (2005). Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann. Surg. Oncol. 12, 1005-1016.
92. Malchow, S., Leventhal, D. S., Nishi, S., Fischer, B. I., Shen, L., Paner, G. P., et al. (2013). Aire-dependent thymic development of tumor-associated regulatory T cells. Science 339, 1219-1224.
93. Mathew, M., Tam, M., Ott, P. A., Pavlick, A. C., Rush, S. C., Donahue, B. R., et al. (2013). Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery. Melanoma Res. 23, 191-195.
94. McCoy, K. D., and Le Gros, G. (1999). The role of CTLA-4 in the regulation of T cell immune responses. Immunol. Cell Biol. 77, 1-10.
95. Medina-Echeverz, J., Fioravanti, J., Zabala, M., Ardaiz, N., Prieto, J., and Berraondo, P. (2011). Successful colon cancer eradication after chemoimmunotherapy is associated with profound phenotypic change of intratumoral myeloid cells. J. Immunol. 186, 807-815.
96. Mellor, A. L., Keskin, D. B., Johnson, T., Chandler, P., and Munn, D. H. (2002). Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses. J. Immunol. 168, 3771-3776.
97. Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J., and Bradfield, C. A. (2010). An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J. Immunol. 185, 3190-3198.
98. Miller, A. M., Lundberg, K., Ozenci, V., Banham, A. H., Hellstrom, M., Egevad, L., et al. (2006). CD4+CD25 high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J. Immunol. 177, 7398-7405.
99. Mitchell, D. A., Cui, X., Schmittling, R. J., Sanchez-Perez, L., Snyder, D. J., Congdon, K. L., et al. (2011). Monoclonal antibody blockade of IL-2 receptor alpha during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood 118, 3003-3012.
100. Mitchell, L., Thamm, D. H., and Biller, B. J. (2012). Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. J. Vet. Intern. Med. 26, 355-362.
101. Mitsuka, K., Kawataki, T., Satoh, E., Asahara, T., Horikoshi, T., and Kinouchi, H. (2013). Expression of Indoleamine 2,3-dioxygenase and Correlation with Pathological Malignancy in Gliomas. Neurosurgery. PMID: 23426156. [Epub ahead of print].
102. Miyazaki, T., Moritake, K., Yamada, K., Hara, N., Osago, H., Shibata, T., et al. (2009). Indoleamine 2,3-dioxygenase as a new target for malignant glioma therapy. Laboratory investigation. J. Neurosurg. 111, 230-237.
103. Mkrtichyan, M., Najjar, Y. G., Raulfs, E. C., Abdalla, M. Y., Samara, R., Rotem-Yehudar, R., et al. (2011). Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms. Eur. J. Immunol. 41, 2977-2986.
104. Munn, D. H., Sharma, M. D., Hou, D., Baban, B., Lee, J. R., Antonia, S. J., et al. (2004). Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J. Clin. Invest. 114, 280-290.
105. Nagasawa, D. T., Chow, F., Yew, A., Kim, W., Cremer, N., and Yang, I. (2012). Temozolomide and other potential agents for the treatment of glioblastoma multiforme. Neurosurg. Clin. N. Am. 23, 307-322.
106. Nair, S., Boczkowski, D., Fassnacht, M., Pisetsky, D., and Gilboa, E. (2007). Vaccination against the forkhead family transcription factor FOXP3 enhances tumor immunity. Cancer Res. 67, 371-380.
107. Nakahara, T., Uchi, H., Lesokhin, A. M., Avogadri, F., Rizzuto, G. A., Hirschhorn-Cymerman, D., et al. (2010). Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood 115, 4384-4392.
108. Nishikawa, H., Kato, T., Tanida, K., Hiasa, A., Tawara, I., Ikeda, H., et al. (2003). CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc. Natl. Acad. Sci. U.S.A. 100, 10902-10906.
109. Onizuka, S., Tawara, I., Shimizu, J., Sakaguchi, S., Fujita, T., and Nakayama, E. (1999). Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 59, 3128-3133.
110. Onodera, T., Jang, M. H., Guo, Z., Yamasaki, M., Hirata, T., Bai, Z., et al. (2009). Constitutive expression of IDO by dendritic cells of mesenteric lymph nodes: functional involvement of the CTLA-4/B7 and CCL22/CCR4 interactions. J. Immunol. 183, 5608-5614.
111. Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., et al. (2011). An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478, 197-203.
112. Pacholczyk, R., Ignatowicz, H., Kraj, P., and Ignatowicz, L. (2006). Origin and T cell receptor diversity of FOXP3+CD4+CD25+ T cells. Immunity 25, 249-259.
113. Pallotta, M. T., Orabona, C., Volpi, C., Vacca, C., Belladonna, M. L., Bianchi, R., et al. (2011). Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat. Immunol. 12, 870-878.
114. Peng, S., Lyford-Pike, S., Akpeng, B., Wu, A., Hung, C. F., Hannaman, D., et al. (2013). Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine. Cancer Immunol. Immunother. 62, 171-182.
115. Pere, H., Montier, Y., Bayry, J., Quintin-Colonna, F., Merillon, N., Dransart, E., et al. (2011). A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens. Blood 118, 4853-4862.
116. Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., et al. (2003). Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. U.S.A. 100, 8372-8377.
117. Piconese, S., Valzasina, B., and Colombo, M. P. (2008). OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J. Exp. Med. 205, 825-839.
118. Plautz, G. E., Miller, D. W., Barnett, G. H., Stevens, G. H., Maffett, S., Kim, J., et al. (2000). T cell adoptive immunotherapy of newly diagnosed gliomas. Clin. Cancer Res. 6, 2209-2218.
119. Poirier, M. D., Haban, H., and El Andaloussi, A. (2009). A combination of systemic and intracranial anti-CD25 immunotherapy elicits a long-time survival in murine model of glioma. J. Oncol. 2009, 963037.
120. Poljak, A., Grant, R., Austin, C. J., Jamie, J. F., Willows, R. D., Takikawa, O., et al. (2006). Inhibition of indoleamine 2,3 dioxygenase activity by H2O2. Arch. Biochem. Biophys. 450, 9-19.
121. Powell, D. J. Jr., Felipe-Silva, A., Merino, M. J., Ahmadzadeh, M., Allen, T., Levy, C., et al. (2007). Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo. J. Immunol. 179, 4919-4928.
122. Qian, F., Liao, J., Villella, J., Edwards, R., Kalinski, P., Lele, S., et al. (2012). Effects of 1-methyltryptophan stereoisomers on IDO2 enzyme activity and IDO2-mediated arrest of human T cell proliferation. Cancer Immunol. Immunother. 61, 2013-2020.
123. Quezada, S. A., Peggs, K. S., Simpson, T. R., and Allison, J. P. (2011). Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol. Rev. 241, 104-118.
124. Quintana, F. J., Basso, A. S., Iglesias, A. H., Korn, T., Farez, M. F., Bettelli, E., et al. (2008). Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65-71.
125. Radojcic, V., Bezak, K. B., Skarica, M., Pletneva, M. A., Yoshimura, K., Schulick, R. D., et al. (2010). Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination. Cancer Immunol. Immunother. 59, 137-148.
126. Rubtsov, Y. P., Niec, R. E., Josefowicz, S., Li, L., Darce, J., Mathis, D., et al. (2010). Stability of the regulatory T cell lineage in vivo. Science 329, 1667-1671.
127. Rudd, C. E. (2008). The reverse stop-signal model for CTLA4 function. Nat. Rev. Immunol. 8, 153-160.
128. Sampson, J. H., Schmittling, R. J., Archer, G. E., Congdon, K. L., Nair, S. K., Reap, E. A., et al. (2012). A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS ONE 7:e31046. doi:10.1371/journal.pone.0031046
129. Samstein, R. M., Josefowicz, S. Z., Arvey, A., Treuting, P. M., and Rudensky, A. Y. (2012). Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell 150, 29-38.
130. Savage, P. A., Malchow, S., and Leventhal, D. S. (2013). Basic principles of tumor-associated regulatory T cell biology. Trends Immunol. 34, 33-40.
131. Sebastiani, S., Allavena, P., Albanesi, C., Nasorri, F., Bianchi, G., Traidl, C., et al. (2001). Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. J. Immunol. 166, 996-1002.
132. Shannon, P., Sabha, N., Lau, N., Kamnasaran, D., Gutmann, D. H., and Guha, A. (2005). Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model. Am. J. Pathol. 167, 859-867.
133. Sharabi, A., Laronne-Bar-On, A., Meshorer, A., and Haran-Ghera, N. (2010). Chemoimmunotherapy reduces the progression of multiple myeloma in a mouse model. Cancer Prev. Res. (Phila.) 3, 1265-1276.
134. Sharma, M. D., Baban, B., Chandler, P., Hou, D. Y., Singh, N., Yagita, H., et al. (2007). Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J. Clin. Invest. 117, 2570-2582.
135. Shevach, E. M., and Stephens, G. L. (2006). The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity? Nat. Rev. Immunol. 6, 613-618.
136. Shimizu, J., Yamazaki, S., and Sakaguchi, S. (1999). Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 163, 5211-5218.
137. Singer, A., Adoro, S., and Park, J. H. (2008). Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat. Rev. Immunol. 8, 788-801.
138. Stupp, R., Mason, W. P., Van Den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., et al. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987-996.
139. Su, Y. B., Sohn, S., Krown, S. E., Livingston, P. O., Wolchok, J. D., Quinn, C., et al. (2004). Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a toxicity with therapeutic implications. J. Clin. Oncol. 22, 610-616.
140. Taniguchi, T., Hirata, F., and Hayaishi, O. (1977). Intracellular utilization of superoxide anion by indoleamine 2,3-dioxygenase of rabbit enterocytes. J. Biol. Chem. 252, 2774-2776.
141. Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., et al. (2010). Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced FOXP3+ T regulatory cells. J. Immunol. 184, 3433-3441.
142. Topfer, K., Kempe, S., Muller, N., Schmitz, M., Bachmann, M., Cartellieri, M., et al. (2011). Tumor evasion from T cell surveillance. J. Biomed. Biotechnol. 2011, 918471.
143. Turk, M. J., Guevara-Patino, J. A., Rizzuto, G. A., Engelhorn, M. E., Sakaguchi, S., and Houghton, A. N. (2004). Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J. Exp. Med. 200, 771-782.
144. Ueda, R., Fujita, M., Zhu, X., Sasaki, K., Kastenhuber, E. R., Kohanbash, G., et al. (2009). Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin. Cancer Res. 15, 6551-6559.
145. Uyttenhove, C., Pilotte, L., Theate, I., Stroobant, V., Colau, D., Parmentier, N., et al. (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 9, 1269-1274.
146. Valzasina, B., Guiducci, C., Dislich, H., Killeen, N., Weinberg, A. D., and Colombo, M. P. (2005). Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood 105, 2845-2851.
147. Valzasina, B., Piconese, S., Guiducci, C., and Colombo, M. P. (2006). Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. Cancer Res. 66, 4488-4495.
148. Verhagen, J., Genolet, R., Britton, G. J., Stevenson, B. J., Sabatos-Peyton, C. A., Dyson, J., et al. (2013). CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire. Proc. Natl. Acad. Sci. U.S.A. 110, E221-230.
149. Vermeij, R., Leffers, N., Hoogeboom, B. N., Hamming, I. L., Wolf, R., Reyners, A. K., et al. (2012). Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: a single-arm phase II study. Int. J. Cancer 131, E670-680.
150. Vogel, C. F., Nishimura, N., Sciullo, E., Wong, P., Li, W., and Matsumura, F. (2007a). Modulation of the chemokines KC and MCP-1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. Arch. Biochem. Biophys. 461, 169-175.
151. Vogel, C. F., Sciullo, E., Li, W., Wong, P., Lazennec, G., and Matsumura, F. (2007b). RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol. Endocrinol. 21, 2941-2955.
152. Vogel, C. F., Sciullo, E., and Matsumura, F. (2007c). Involvement of RelB in aryl hydrocarbon receptor-mediated induction of chemokines. Biochem. Biophys. Res. Commun. 363, 722-726.
153. Wainwright, D. A., Balyasnikova, I. V., Chang, A. L., Ahmed, A. U., Moon, K. S., Auffinger, B., et al. (2012). IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin. Cancer Res. 18, 6110-6121.
154. Wainwright, D. A., Sengupta, S., Han, Y., and Lesniak, M. S. (2011). Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro-oncology 13, 1308-1323.
155. Wainwright, D. A., Sengupta, S., Han, Y., Ulasov, I. V., and Lesniak, M. S. (2010). The presence of IL-17A and T helper 17 cells in experimental mouse brain tumors and human glioma. PLoS ONE 5:e15390. doi:10.1371/journal.pone.0015390
156. Walker, M. R., Kasprowicz, D. J., Gersuk, V. H., Benard, A., Van Landeghen, M., Buckner, J. H., et al. (2003). Induction of FOXP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest. 112, 1437-1443.
157. Wilgenhof, S., Four, S. D., Vandenbroucke, F., Everaert, H., Salmon, I., Lienard, D., et al. (2013). Single-center experience with ipilimumab in an expanded access program for patients with pretreated advanced melanoma. J. Immunother. 36, 215-222.
158. Wong, J., Mathis, D., and Benoist, C. (2007). TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J. Exp. Med. 204, 2039-2045.
159. Wu, Q., Zhan, X., Dou, T., Chen, H., Fan, W., Zhou, K., et al. (2011). CTLA4 A49G polymorphism shows significant association with glioma risk in a Chinese population. Biochem. Genet. 49, 190-201.
160. Yao, Z., Kanno, Y., Kerenyi, M., Stephens, G., Durant, L., Watford, W. T., et al. (2007). Nonredundant roles for Stat5a/b in directly regulating FOXP3. Blood 109, 4368-4375.
161. Yasui, H., Takai, K., Yoshida, R., and Hayaishi, O. (1986). Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine 2,3-dioxygenase: its possible occurrence in cancer patients. Proc. Natl. Acad. Sci. U.S.A. 83, 6622-6626.
162. Yoshida, R., and Hayaishi, O. (1978). Induction of pulmonary indoleamine 2,3-dioxygenase by intraperitoneal injection of bacterial lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A. 75, 3998-4000.
163. Yoshida, R., Park, S. W., Yasui, H., and Takikawa, O. (1988). Tryptophan degradation in transplanted tumor cells undergoing rejection. J. Immunol. 141, 2819-2823.
164. Zhao, J., Cao, Y., Lei, Z., Yang, Z., Zhang, B., and Huang, B. (2010). Selective depletion of CD4+CD25+Foxp3+ regulatory T cells by low-dose cyclophosphamide is explained by reduced intracellular ATP levels. Cancer Res. 70, 4850-4858.
165. Zhou, G., and Levitsky, H. I. (2007). Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J. Immunol. 178, 2155-2162.
166. Ziegler, S. F. (2006). FOXP3: of mice and men. Annu. Rev. Immunol. 24, 209-226.
167. Zlotnik, A., and Yoshie, O. (2012). The chemokine superfamily revisited. Immunity 36, 705-716.
168. Zorn, E., Nelson, E. A., Mohseni, M., Porcheray, F., Kim, H., Litsa, D., et al. (2006). IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 108, 1571-1579.