Skip to main content
Erschienen in: Breast Cancer Research and Treatment 1/2011

01.05.2011 | Preclinical study

An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

verfasst von: Sahar M. A. Mahmoud, Emma C. Paish, Desmond G. Powe, R. Douglas Macmillan, Andrew H. S. Lee, Ian O. Ellis, Andrew R. Green

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Studies in mice have shown that thymic-derived CD4+ CD25+ regulatory T cells (T reg; FOXP3+ lymphocytes) inhibit an antitumour immune response. Additional studies have also reported that the T reg population increases in peripheral blood and tumour tissues from patients with cancer. However, the relationship between the T reg population and the patient prognosis remains controversial. Our aim was to determine the prognostic value of T reg cell density in breast cancer using immunohistochemical assessment of FOXP3, which has been shown to be the optimal marker for T regs. Tissue microarrays were used, and the density of FOXP3+ cells was determined in a series of 1445 cases of well-characterised primary invasive breast carcinoma cases with long-term follow up. FOXP3+ cell numbers were counted in tumour nests, in tumour-adjacent stroma, and in distant stroma. The total number of FOXP3+ cells significantly correlated with higher tumour grade (r s = 0.37, P < 0.001) and ER negativity (Mann–Whitney U test, P < 0.001). In addition, FOXP3 infiltration positively correlated with HER2 expression and basal phenotype subclass. On univariate analysis, FOXP3+ cells were associated with a worse prognosis (P = 0.012, log rank = 6.36). This association was found for intratumoural FOXP3+ and for tumour-adjacent stromal FOXP3+-cells (tumour-cell associated FOXP3, P = 0.001 and log rank 10.35). However, the number of FOXP3+ cells was not found to be an independent prognostic factor in multivariate analysis. We therefore conclude that FOXP3+ infiltrating cells do not have a dominant role in breast cancer prognosis and suggest that other inflammatory cell subsets may be more critical variables.
Literatur
1.
Zurück zum Zitat Callagy G, Cattaneo E, Daigo Y, Happerfield L, Bobrow LG, Pharoah PD et al (2003) Molecular classification of breast carcinomas using tissue microarrays. Diagn Mol Pathol 12(1):27–34PubMedCrossRef Callagy G, Cattaneo E, Daigo Y, Happerfield L, Bobrow LG, Pharoah PD et al (2003) Molecular classification of breast carcinomas using tissue microarrays. Diagn Mol Pathol 12(1):27–34PubMedCrossRef
2.
Zurück zum Zitat Stewart TH, Heppner GH (1997) Immunological enhancement of breast cancer. Parasitology 115:S141–S153PubMedCrossRef Stewart TH, Heppner GH (1997) Immunological enhancement of breast cancer. Parasitology 115:S141–S153PubMedCrossRef
3.
Zurück zum Zitat Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR (2006) Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 48(6):692–701PubMedCrossRef Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR (2006) Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 48(6):692–701PubMedCrossRef
4.
Zurück zum Zitat Rilke F, Colnaghi MI, Cascinelli N, Andreola S, Baldini MT, Bufalino R et al (1991) Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors. Int J Cancer 49(1):44–49PubMedCrossRef Rilke F, Colnaghi MI, Cascinelli N, Andreola S, Baldini MT, Bufalino R et al (1991) Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors. Int J Cancer 49(1):44–49PubMedCrossRef
5.
Zurück zum Zitat Carlomagno C, Perrone F, Lauria R, de Laurentiis M, Gallo C, Morabito A et al (1995) Prognostic significance of necrosis, elastosis, fibrosis and inflammatory cell reaction in operable breast cancer. Oncology 52(4):272–277PubMedCrossRef Carlomagno C, Perrone F, Lauria R, de Laurentiis M, Gallo C, Morabito A et al (1995) Prognostic significance of necrosis, elastosis, fibrosis and inflammatory cell reaction in operable breast cancer. Oncology 52(4):272–277PubMedCrossRef
6.
Zurück zum Zitat Yu P, Fu YX (2006) Tumor-infiltrating T lymphocytes: friends or foes? Lab Invest 86(3):231–245PubMedCrossRef Yu P, Fu YX (2006) Tumor-infiltrating T lymphocytes: friends or foes? Lab Invest 86(3):231–245PubMedCrossRef
7.
Zurück zum Zitat Sprent J, Surh CD (2003) Knowing one’s self: central tolerance revisited. Nat Immunol 4(4):303–304PubMedCrossRef Sprent J, Surh CD (2003) Knowing one’s self: central tolerance revisited. Nat Immunol 4(4):303–304PubMedCrossRef
8.
9.
Zurück zum Zitat Buckner JH, Ziegler SF (2004) Regulating the immune system: the induction of regulatory T cells in the periphery. Arthritis Res Ther 6(5):215–222PubMedCrossRef Buckner JH, Ziegler SF (2004) Regulating the immune system: the induction of regulatory T cells in the periphery. Arthritis Res Ther 6(5):215–222PubMedCrossRef
10.
Zurück zum Zitat Kosmaczewska A, Ciszak L, Potoczek S, Frydecka I (2008) The significance of Treg cells in defective tumor immunity. Arch Immunol Ther Exp (Warsz) 56(3):181–191CrossRef Kosmaczewska A, Ciszak L, Potoczek S, Frydecka I (2008) The significance of Treg cells in defective tumor immunity. Arch Immunol Ther Exp (Warsz) 56(3):181–191CrossRef
11.
Zurück zum Zitat Ramsdell F (2003) Foxp3 and natural regulatory T cells: key to a cell lineage? Immunity 19(2):165–168PubMedCrossRef Ramsdell F (2003) Foxp3 and natural regulatory T cells: key to a cell lineage? Immunity 19(2):165–168PubMedCrossRef
12.
Zurück zum Zitat Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193(11):1303–1310PubMedCrossRef Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193(11):1303–1310PubMedCrossRef
13.
Zurück zum Zitat Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G 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(5):2756–2761PubMed Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G 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(5):2756–2761PubMed
14.
Zurück zum Zitat Sakaguchi S (2000) Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101(5):455–458PubMedCrossRef Sakaguchi S (2000) Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101(5):455–458PubMedCrossRef
15.
Zurück zum Zitat Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3):329–341PubMedCrossRef Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3):329–341PubMedCrossRef
16.
Zurück zum Zitat Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061PubMedCrossRef Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061PubMedCrossRef
17.
Zurück zum Zitat Roncador G, Brown PJ, Maestre L, Hue S, Martinez-Torrecuadrada JL, Ling KL et al (2005) Analysis of FOXP3 protein expression in human CD4+ CD25+ regulatory T cells at the single-cell level. Eur J Immunol 35(6):1681–1691PubMedCrossRef Roncador G, Brown PJ, Maestre L, Hue S, Martinez-Torrecuadrada JL, Ling KL et al (2005) Analysis of FOXP3 protein expression in human CD4+ CD25+ regulatory T cells at the single-cell level. Eur J Immunol 35(6):1681–1691PubMedCrossRef
18.
Zurück zum Zitat Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59(13):3128–3133PubMed Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59(13):3128–3133PubMed
19.
Zurück zum Zitat Shimizu J, Yamazaki S, Sakaguchi S (1999) Induction of tumor immunity by removing CD25+ CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 163(10):5211–5218PubMed Shimizu J, Yamazaki S, Sakaguchi S (1999) Induction of tumor immunity by removing CD25+ CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 163(10):5211–5218PubMed
20.
Zurück zum Zitat Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP et al (2001) Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 194(6):823–832PubMedCrossRef Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP et al (2001) Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 194(6):823–832PubMedCrossRef
21.
Zurück zum Zitat Tanaka H, Tanaka J, Kjaergaard J, Shu S (2002) Depletion of CD4+ CD25+ regulatory cells augments the generation of specific immune T cells in tumor-draining lymph nodes. J Immunother 25(3):207–217PubMedCrossRef Tanaka H, Tanaka J, Kjaergaard J, Shu S (2002) Depletion of CD4+ CD25+ regulatory cells augments the generation of specific immune T cells in tumor-draining lymph nodes. J Immunother 25(3):207–217PubMedCrossRef
22.
Zurück zum Zitat Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL et al (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24(34):5373–5380PubMedCrossRef Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL et al (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24(34):5373–5380PubMedCrossRef
23.
Zurück zum Zitat 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(9):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(9):942–949PubMedCrossRef
24.
Zurück zum Zitat 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. 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. Clin Cancer Res 9(2):606–612PubMed
25.
Zurück zum Zitat Hiraoka N, Onozato K, Kosuge T, Hirohashi S (2006) Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 12(18):5423–5434PubMedCrossRef Hiraoka N, Onozato K, Kosuge T, Hirohashi S (2006) Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 12(18):5423–5434PubMedCrossRef
26.
Zurück zum Zitat Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr et al (2006) Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 107(12):2866–2872PubMedCrossRef Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr et al (2006) Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 107(12):2866–2872PubMedCrossRef
27.
Zurück zum Zitat Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS et al (2007) Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25(18):2586–2593PubMedCrossRef Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS et al (2007) Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25(18):2586–2593PubMedCrossRef
28.
Zurück zum Zitat Yoshioka T, Miyamoto M, Cho Y, Ishikawa K, Tsuchikawa T, Kadoya M et al (2008) Infiltrating regulatory T cell numbers is not a factor to predict patient’s survival in oesophageal squamous cell carcinoma. Br J Cancer 98(7):1258–1263PubMedCrossRef Yoshioka T, Miyamoto M, Cho Y, Ishikawa K, Tsuchikawa T, Kadoya M et al (2008) Infiltrating regulatory T cell numbers is not a factor to predict patient’s survival in oesophageal squamous cell carcinoma. Br J Cancer 98(7):1258–1263PubMedCrossRef
29.
Zurück zum Zitat Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D et al (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27(2):186–192PubMedCrossRef Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D et al (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27(2):186–192PubMedCrossRef
30.
Zurück zum Zitat Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B et al (2008) Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells. Clin Cancer Res 14(8):2413–2420PubMedCrossRef Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B et al (2008) Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells. Clin Cancer Res 14(8):2413–2420PubMedCrossRef
31.
Zurück zum Zitat Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF et al (2005) High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116(3):340–350PubMedCrossRef Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF et al (2005) High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116(3):340–350PubMedCrossRef
32.
Zurück zum Zitat Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF et al (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203(2):661–671PubMedCrossRef Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF et al (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203(2):661–671PubMedCrossRef
33.
Zurück zum Zitat Rakha EA, El-Rehim DA, Paish C, Green AR, Lee AH, Robertson JF et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42(18):3149–3156PubMedCrossRef Rakha EA, El-Rehim DA, Paish C, Green AR, Lee AH, Robertson JF et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42(18):3149–3156PubMedCrossRef
34.
Zurück zum Zitat Zhang H, Rakha EA, Ball GR, Spiteri I, Aleskandarany M, Paish EC et al (2010) The proteins FABP7 and OATP2 are associated with the basal phenotype and patient outcome in human breast cancer. Breast Cancer Res Treat 121(1):41–51PubMedCrossRef Zhang H, Rakha EA, Ball GR, Spiteri I, Aleskandarany M, Paish EC et al (2010) The proteins FABP7 and OATP2 are associated with the basal phenotype and patient outcome in human breast cancer. Breast Cancer Res Treat 121(1):41–51PubMedCrossRef
35.
Zurück zum Zitat Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410PubMedCrossRef Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410PubMedCrossRef
36.
Zurück zum Zitat Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 20(6):479–489PubMedCrossRef Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 20(6):479–489PubMedCrossRef
37.
Zurück zum Zitat Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24(1):41–47PubMedCrossRef Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24(1):41–47PubMedCrossRef
38.
Zurück zum Zitat Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219PubMedCrossRef Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219PubMedCrossRef
39.
Zurück zum Zitat Green AR, Burney C, Granger CJ, Paish EC, El-Sheikh S, Rakha EA et al (2008) The prognostic significance of steroid receptor co-regulators in breast cancer: co-repressor NCOR2/SMRT is an independent indicator of poor outcome. Breast Cancer Res Treat 110(3):427–437PubMedCrossRef Green AR, Burney C, Granger CJ, Paish EC, El-Sheikh S, Rakha EA et al (2008) The prognostic significance of steroid receptor co-regulators in breast cancer: co-repressor NCOR2/SMRT is an independent indicator of poor outcome. Breast Cancer Res Treat 110(3):427–437PubMedCrossRef
40.
Zurück zum Zitat McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072PubMedCrossRef McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072PubMedCrossRef
41.
Zurück zum Zitat Rakha EA, El-Sheikh SE, Kandil MA, El-Sayed ME, Green AR, Ellis IO (2008) Expression of BRCA1 protein in breast cancer and its prognostic significance. Hum Pathol 39(6):857–865PubMedCrossRef Rakha EA, El-Sheikh SE, Kandil MA, El-Sayed ME, Green AR, Ellis IO (2008) Expression of BRCA1 protein in breast cancer and its prognostic significance. Hum Pathol 39(6):857–865PubMedCrossRef
42.
Zurück zum Zitat Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21):7252–7259PubMedCrossRef Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21):7252–7259PubMedCrossRef
43.
Zurück zum Zitat Dolled-Filhart M, McCabe A, Giltnane J, Cregger M, Camp RL, Rimm DL (2006) Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome. Cancer Res 66(10):5487–5494PubMedCrossRef Dolled-Filhart M, McCabe A, Giltnane J, Cregger M, Camp RL, Rimm DL (2006) Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome. Cancer Res 66(10):5487–5494PubMedCrossRef
44.
Zurück zum Zitat Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32PubMedCrossRef Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32PubMedCrossRef
45.
Zurück zum Zitat 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(3):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(3):1151–1164PubMed
46.
Zurück zum Zitat Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307PubMedCrossRef Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307PubMedCrossRef
47.
Zurück zum Zitat Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H et al (2006) Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12(2):465–472PubMedCrossRef Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H et al (2006) Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12(2):465–472PubMedCrossRef
48.
Zurück zum Zitat Carreras J, Lopez-Guillermo A, Fox BC, Colomo L, Martinez A, Roncador G et al (2006) High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood 108(9):2957–2964PubMedCrossRef Carreras J, Lopez-Guillermo A, Fox BC, Colomo L, Martinez A, Roncador G et al (2006) High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood 108(9):2957–2964PubMedCrossRef
49.
Zurück zum Zitat Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11(23):8326–8331PubMedCrossRef Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11(23):8326–8331PubMedCrossRef
50.
Zurück zum Zitat Grabenbauer GG, Lahmer G, Distel L, Niedobitek G (2006) Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin Cancer Res 12(11 Pt 1):3355–3360PubMedCrossRef Grabenbauer GG, Lahmer G, Distel L, Niedobitek G (2006) Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin Cancer Res 12(11 Pt 1):3355–3360PubMedCrossRef
51.
Zurück zum Zitat Bohling SD, Allison KH (2008) Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 21(12):1527–1532PubMedCrossRef Bohling SD, Allison KH (2008) Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 21(12):1527–1532PubMedCrossRef
52.
Zurück zum Zitat Ghebeh H, Barhoush E, Tulbah A, Elkum N, Al-Tweigeri T, Dermime S (2008) FOXP3+ Tregs and B7–H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy. BMC Cancer 8:57PubMedCrossRef Ghebeh H, Barhoush E, Tulbah A, Elkum N, Al-Tweigeri T, Dermime S (2008) FOXP3+ Tregs and B7–H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy. BMC Cancer 8:57PubMedCrossRef
53.
Zurück zum Zitat Ahmadzadeh M, Felipe-Silva A, Heemskerk B, Powell DJ Jr, Wunderlich JR, Merino MJ et al (2008) FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions. Blood 112(13):4953–4960PubMedCrossRef Ahmadzadeh M, Felipe-Silva A, Heemskerk B, Powell DJ Jr, Wunderlich JR, Merino MJ et al (2008) FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions. Blood 112(13):4953–4960PubMedCrossRef
54.
Zurück zum Zitat Hinz S, Pagerols-Raluy L, Oberg HH, Ammerpohl O, Grussel S, Sipos B et al (2007) Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res 67(17):8344–8350PubMedCrossRef Hinz S, Pagerols-Raluy L, Oberg HH, Ammerpohl O, Grussel S, Sipos B et al (2007) Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res 67(17):8344–8350PubMedCrossRef
55.
Zurück zum Zitat Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T et al (2008) Foxp3 expression in human cancer cells. J Transl Med 6:19PubMedCrossRef Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T et al (2008) Foxp3 expression in human cancer cells. J Transl Med 6:19PubMedCrossRef
Metadaten
Titel
An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer
verfasst von
Sahar M. A. Mahmoud
Emma C. Paish
Desmond G. Powe
R. Douglas Macmillan
Andrew H. S. Lee
Ian O. Ellis
Andrew R. Green
Publikationsdatum
01.05.2011
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2011
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-0987-8

Weitere Artikel der Ausgabe 1/2011

Breast Cancer Research and Treatment 1/2011 Zur Ausgabe

Alter verschlechtert Prognose bei Endometriumkarzinom

11.05.2024 Endometriumkarzinom Nachrichten

Ein höheres Alter bei der Diagnose eines Endometriumkarzinoms ist mit aggressiveren Tumorcharakteristika assoziiert, scheint aber auch unabhängig von bekannten Risikofaktoren die Prognose der Erkrankung zu verschlimmern.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.