Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy

PLoS ONE

Volumn 7, Issue 10, 2012, Pages

  Schwarzer, Adrian ^a   Wolf, Benita ^a   Fisher, Jan L ^a   Schwaab, Thomas ^a   Olek, Sven ^b   Baron, Udo ^b   Tomlinson, Craig R ^a   Seigne, John D ^a   Crosby, Nancy A ^a   Gui, Jiang ^a   Hampton, Thomas H ^a   Fadul, Camilo E ^a   Heaney, John A ^a   Ernstoff, Marc S ^a  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

^b EPIONTIS GMBH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA2A INTERFERON; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DENDRITIC CELL VACCINE; INTERLEUKIN 2; RNA; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ADVANCED CANCER; ARTICLE; CANCER IMMUNIZATION; CANCER PATIENT; CD3+ T LYMPHOCYTE; CD4+ CD25+ FOXP3+ REGULATORY T LYMPHOCYTE; CELL EXPANSION; CLINICAL ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DENDRITIC CELL; DISEASE ASSOCIATION; DNA METHYLATION; DNA MICROARRAY; DRUG MEGADOSE; EPIGENETICS; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION PROFILING; GENE TARGETING; HUMAN; HUMAN CELL; IMMUNOREGULATION; IMMUNOTHERAPY; KIDNEY METASTASIS; LYMPHOCYTE COUNT; MALE; MULTIPLE CYCLE TREATMENT; NUCLEOTIDE SEQUENCE; PERIPHERAL LYMPHOCYTE; PHENOTYPE; POLYMERASE CHAIN REACTION; QUANTITATIVE ANALYSIS; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TRANSCRIPTOMICS; TREATMENT OUTCOME;

CARCINOMA, RENAL CELL; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; CTLA-4 ANTIGEN; DNA METHYLATION; FEMALE; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION PROFILING; HUMANS; IMMUNOTHERAPY; INTERLEUKIN-2; MALE; METABOLIC NETWORKS AND PATHWAYS; NEOPLASM METASTASIS; NEOPLASTIC CELLS, CIRCULATING; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA; VACCINATION;

EID: 84868280132     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0046600     Document Type: Article

References (43)

1. Atkins MB, Sparano J, Fisher RI, Weiss GR, Margolin KA, et al. (1993) Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 11: 661-670.
2. Motzer RJ, Mazumdar M, Bacik J, Russo P, Berg WJ, et al. (2000) Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 18: 1928-1935.
3. Atzpodien J, Kirchner H, Jonas U, Bergmann L, Schott H, et al. (2004) Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Journal of clinical oncology: official journal of the American Society of Clinical Oncology 22: 1188-1194.
4. Cesana GC, (2006) Characterization of CD4+CD25+ Regulatory T Cells in Patients Treated With High-Dose Interleukin-2 for Metastatic Melanoma or Renal Cell Carcinoma. Journal of Clinical Oncology 24: 1169-1177.
5. Yao X, Ahmadzadeh M, Lu YC, Liewehr DJ, Dudley ME, et al. (2012) Levels of peripheral CD4+FoxP3+ regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer. Blood 119: 5688-5696.
6. Jacobs JF, Nierkens S, Figdor CG, de Vries IJ, Adema GJ, (2012) Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy? The lancet oncology 13: e32-42.
7. Wang Y, Ma Y, Fang Y, Wu S, Liu L, et al. (2012) Regulatory T cell: a protection for tumour cells. Journal of cellular and molecular medicine 16: 425-436.
8. Onishi H, Morisaki T, Katano M, (2012) Immunotherapy approaches targeting regulatory T-cells. Anticancer research 32: 997-1003.
9. Schwaab T, Schwarzer A, Wolf B, Crocenzi TS, Seigne JD, et al. (2009) Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients. Clinical cancer research: an official journal of the American Association for Cancer Research 15: 4986-4992.
10. Sakaguchi S, (2004) Naturally Arising CD4+ Regulatory T Cells for Immunologic Self-Tolerance and Negative Control of Immune Responses. Annual Review of Immunology 22: 531-562.
11. Yi H, Zhen Y, Jiang L, Zheng J, Zhao Y, (2006) The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells. Cellular & molecular immunology 3: 189-195.
12. Lafaille MACd, Lafaille JJ, (2009) Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor? Immunity 30: 626-635.
13. Ziegler S, (2006) FOXP3: Of Mice and Men. Annu Rev Immunol 24: 209-226.
14. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, et al. (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22: 329-341.
15. Hori S, Nomura T, Sakaguchi S, (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061.
16. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, et al. (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27: 20-21.
17. Zou W, (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5: 263-274.
18. Cesana G, (2006) Characterization of CD4+CD25+ Regulatory T Cells in Patients Treated With High-Dose Interleukin-2 for Metastatic Melanoma or Renal Cell Carcinoma. Journal of Clinical Oncology 24: 1169-1177.
19. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, et al. (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169: 2756-2761.
20. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, et al. (2003) Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 9: 606-612.
21. Ahmadzadeh M, Rosenberg SA, (2006) IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood 107: 2409-2414.
22. Zorn E, (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.
23. Schwaab T, Schwarzer A, Wolf B, Crocenzi T, Seigne J, et al. (2009) Clinical and Immunologic Effects of Intranodal Autologous Tumor Lysate-Dendritic Cell Vaccine with Aldesleukin (Interleukin 2) and IFN- 2a Therapy in Metastatic Renal Cell Carcinoma Patients. Clinical Cancer Research 15: 4986-4992.
24. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY, (2005) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nature Immunology 6: 1142-1151.
25. Sakaguchi S, Miyara M, Costantino CM, Hafler DA, (2010) FOXP3+ regulatory T cells in the human immune system. Nature Reviews Immunology 10: 490-500.
26. Pillai V, Ortega SB, Wang CK, Karandikar NJ, (2007) Transient regulatory T-cells: a state attained by all activated human T-cells. Clinical immunology 123: 18-29.
27. Huehn J, Polansky J, Hamann A, (2009) Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat Rev Immunol 9: 83-89.
28. Baron U, Floess S, Wieczorek G, Baumann K, Grutzkau A, et al. (2007) DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. European journal of immunology 37: 2378-2389.
29. Floess S, Freyer J, Siewert C, Baron U, Olek S, et al. (2007) Epigenetic control of the foxp3 locus in regulatory T cells. PLoS biology 5: e38.
30. Polansky J, Kretschmer K, Freyer J, Floess S, Garbe A, et al. (2008) DNA methylation controls Foxp3 gene expression. Eur J Immunol 38: 1654-1663.
31. Showe M, Vachani A, Kossenkov A, Yousef M, Nichols C, et al. (2009) Gene Expression Profiles in Peripheral Blood Mononuclear Cells Can Distinguish Patients with Non-Small Cell Lung Cancer from Patients with Nonmalignant Lung Disease. Cancer Research 69: 9202-9210.
32. Twine N, (2003) Disease-associated Expression Profiles in Peripheral Blood Mononuclear Cells from Patients with Advanced Renal Cell Carcinoma. Cancer Research pp. 1-8.
33. Team RDC (2010) R: A language and environment for statistical computing. R Foundation for Statistical Computing.
34. Kauffmann A, Gentleman R, Huber W, (2009) arrayQualityMetrics-a bioconductor package for quality assessment of microarray data. Bioinformatics 25: 415-416.
35. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249-264.
36. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102: 15545-15550.
37. Sehouli J, Loddenkemper C, Cornu T, Schwachula T, Hoffmuller U, et al. (2011) Epigenetic quantification of tumor-infiltrating T-lymphocytes. Epigenetics: official journal of the DNA Methylation Society 6: 236-246.
38. Wieczorek G, Asemissen A, Model F, Turbachova I, Floess S, et al. (2009) Quantitative DNA Methylation Analysis of FOXP3 as a New Method for Counting Regulatory T Cells in Peripheral Blood and Solid Tissue. Cancer Research 69: 599-608.
39. Oberg H, Wesch D, Lenke J, Kabelitz D, (2006) An Optimized Method for the Functional Analysis of Human Regulatory T Cells. Scand J Immunol 64: 353-360.
40. Jensen HK, Donskov F, Nordsmark M, Marcussen N, von der Maase H, (2009) Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma. Clin Cancer Res 15: 1052-1058.
41. Tatsugami K, Eto M, Naito S, (2010) Influence of immunotherapy with interferon-alpha on regulatory T cells in renal cell carcinoma patients. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 30: 43-48.
42. Jiang Z, Gentleman R, (2006) Extensions to gene set enrichment. Bioinformatics 23: 306-313.
43. Wolf B, Schwarzer A, Côté A, Hampton T, Schwaab T, et al. (2012) Gene Expression Profile of Peripheral Blood Lymphocytes from Metastatic Renal Cell Cancer Patients treated with IL-2, Interferon-α and Dendritic Cell Vaccine. PLoS ONE.