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Published in: Targeted Oncology 3/2011

01-09-2011 | Original Research

The variation of CD4+CD25+ regulatory T cells in the periphery blood and tumor microenvironment of non-small cell lung cancer patients and the downregulation effects induced by CpG ODN

Authors: Yan-Ying Wang, Xiao-Ye He, Ying-Yun Cai, Zhi-Jun Wang, Shao-Hua Lu

Published in: Targeted Oncology | Issue 3/2011

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Abstract

The aim of the study was to observe the variation of CD4+CD25+ regulatory T cells in periphery blood and tumor microenvironment of non-small cell lung cancer (NSCLC) patients and the effects of CpG ODN. The proportion of CD4+CD25+ regulatory T cells, Foxp3 gene expression, levels of tumor growth factor-β (TGF-β) and immunoreactive fibronectin-γ (IFN-γ) in the periphery blood of 30 NSCLC patients and 30 healthy volunteers were compared. These indicators were compared before and after CpG ODN treatment. Foxp3 gene expression in the tumor microenvironment of NSCLC patients was also observed. The results showed CD4+CD25+ regulatory T cell proportion, Foxp3 expression and TGF-β levels in the periphery blood of NSCLC patients were higher than those of healthy volunteers (p < 0.05), and these indicators of patients were significantly decreased after CpG ODN 2006 treatment (p < 0.05). Foxp3 expression in the metastatic lymph nodes was higher than that in the non-metastatic ones of NSCLC patients (p = 0.000). In conclusion, a rise in the proportion of CD4+CD25+Foxp3+ regulatory T cells was demonstrated in the periphery blood and tumor microenvironments of NSCLC patients. CpG ODN 2006 downregulated the CD4+CD25+Foxp3+ regulatory T cells proportion and TGF-β levels in the periphery blood of these patients.
Literature
1.
go back to reference Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155:1151–1164PubMed Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155:1151–1164PubMed
2.
go back to reference Rudge G, Gleeson PA, van Driel IR (2006) Control of immune responses by immunoregulatory T cells. Arch Immunol Ther Exp (Warsz) 54:381–391CrossRef Rudge G, Gleeson PA, van Driel IR (2006) Control of immune responses by immunoregulatory T cells. Arch Immunol Ther Exp (Warsz) 54:381–391CrossRef
3.
go back to reference Field EH, Matesic D, Rigby S, Fehr T, Rouse T, Gao Q (2001) CD4+CD25+ regulatory cells in acquired MHC tolerance. Immunol Rev 182:99–112PubMedCrossRef Field EH, Matesic D, Rigby S, Fehr T, Rouse T, Gao Q (2001) CD4+CD25+ regulatory cells in acquired MHC tolerance. Immunol Rev 182:99–112PubMedCrossRef
4.
go back to reference Somasundaram R, Jacob L, Swoboda R, Caputo L, Song H, Basak S et al (2002) In–ibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. Cancer Res 62:5267–5272PubMed Somasundaram R, Jacob L, Swoboda R, Caputo L, Song H, Basak S et al (2002) In–ibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. Cancer Res 62:5267–5272PubMed
5.
go back to reference Gajewski TF, Meng Y, Harlin H (2006) Immune suppression in the tumor microenvironment. J Immunother 29:233–240PubMedCrossRef Gajewski TF, Meng Y, Harlin H (2006) Immune suppression in the tumor microenvironment. J Immunother 29:233–240PubMedCrossRef
6.
go back to reference Sfondrini L, Besusso D, Bronte V, Macino B, Rossini A, Colombo MP, Ménard S, Balsari A (2004) CpG-Oligodeoxynucleotides activate tyrosinase-related protein 2-specific T lymphocytes but do not lead to a protective tumor-specific memory response. Cancer Immunol Immunother 53:697–704PubMedCrossRef Sfondrini L, Besusso D, Bronte V, Macino B, Rossini A, Colombo MP, Ménard S, Balsari A (2004) CpG-Oligodeoxynucleotides activate tyrosinase-related protein 2-specific T lymphocytes but do not lead to a protective tumor-specific memory response. Cancer Immunol Immunother 53:697–704PubMedCrossRef
7.
go back to reference Smyth MJ, Teng MW, Swann J, Kyparissoudis K, Godfrey DI, Hayakawa Y (2006) CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol 176:1582–1587PubMed Smyth MJ, Teng MW, Swann J, Kyparissoudis K, Godfrey DI, Hayakawa Y (2006) CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol 176:1582–1587PubMed
8.
go back to reference Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274PubMedCrossRef Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274PubMedCrossRef
9.
go back to reference Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM (2006) The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol Rev 212:60–73PubMedCrossRef Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM (2006) The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol Rev 212:60–73PubMedCrossRef
10.
go back to reference Enarsson K, Johnsson E, Lindholm C, Lundgren A, Pan-HammarstrÖm Q, StrÖmberg E et al (2006) Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa. Clin Immunol 118:24–34PubMedCrossRef Enarsson K, Johnsson E, Lindholm C, Lundgren A, Pan-HammarstrÖm Q, StrÖmberg E et al (2006) Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa. Clin Immunol 118:24–34PubMedCrossRef
11.
go back to reference Curiel TJ, 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 10:942–949PubMedCrossRef Curiel TJ, 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 10:942–949PubMedCrossRef
12.
go back to reference Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B (2003) Increase of regulatory T cells in the peripheral blood of cancer patients [J]. Clin Cancer Res 9(2):606–612PubMed Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B (2003) Increase of regulatory T cells in the peripheral blood of cancer patients [J]. Clin Cancer Res 9(2):606–612PubMed
13.
go back to reference Read S, Malmström V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192(2):295–302PubMedCrossRef Read S, Malmström V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192(2):295–302PubMedCrossRef
14.
go back to reference Nakamura K, Kitani A, Strober W (2001) Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 194:629–644PubMedCrossRef Nakamura K, Kitani A, Strober W (2001) Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 194:629–644PubMedCrossRef
15.
go back to reference Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, You Z, Kaynor C, Wang X, Fu YX (2005) Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 201:779–791PubMedCrossRef Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, You Z, Kaynor C, Wang X, Fu YX (2005) Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 201:779–791PubMedCrossRef
16.
go back to reference Seo N, Hayakawa S, Takigawa M, Tokura Y (2001) Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity. Immunology 103:449–457PubMedCrossRef Seo N, Hayakawa S, Takigawa M, Tokura Y (2001) Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity. Immunology 103:449–457PubMedCrossRef
17.
go back to reference Chen ZM, O’Shaughnessy MJ, Gramaglia I, Panoskaltsis-Mortari A, Murphy WJ, Narula S, Roncarolo MG, Blazar BR (2003) IL-10 and TGF-beta induce alloreactive CD4+CD25- T cells to acquire regulatory cell function. Blood 101:5076–5083PubMedCrossRef Chen ZM, O’Shaughnessy MJ, Gramaglia I, Panoskaltsis-Mortari A, Murphy WJ, Narula S, Roncarolo MG, Blazar BR (2003) IL-10 and TGF-beta induce alloreactive CD4+CD25- T cells to acquire regulatory cell function. Blood 101:5076–5083PubMedCrossRef
18.
go back to reference Vollmer J, Weeratna R, Payette P, Jurk M, Schetter C, Laucht M, Wader T, Tluk S, Liu M, Davis HL, Krieg AM (2004) Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol 34:251–262PubMedCrossRef Vollmer J, Weeratna R, Payette P, Jurk M, Schetter C, Laucht M, Wader T, Tluk S, Liu M, Davis HL, Krieg AM (2004) Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol 34:251–262PubMedCrossRef
19.
go back to reference Law JP, Hirschkorn DF, Owen RE, Biswas HH, Norris PJ, Lanteri MC (2009) The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells. Cytom A 75(12):1040–1050CrossRef Law JP, Hirschkorn DF, Owen RE, Biswas HH, Norris PJ, Lanteri MC (2009) The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells. Cytom A 75(12):1040–1050CrossRef
Metadata
Title
The variation of CD4+CD25+ regulatory T cells in the periphery blood and tumor microenvironment of non-small cell lung cancer patients and the downregulation effects induced by CpG ODN
Authors
Yan-Ying Wang
Xiao-Ye He
Ying-Yun Cai
Zhi-Jun Wang
Shao-Hua Lu
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Targeted Oncology / Issue 3/2011
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-011-0182-9

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