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Erschienen in: Immunologic Research 1/2011

01.10.2011

Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer

verfasst von: Chao-Hsu Li, Wen-Hong Kuo, Wen-Chun Chang, Su-Cheng Huang, King-Jen Chang, Bor-Ching Sheu

Erschienen in: Immunologic Research | Ausgabe 1/2011

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Abstract

Regulatory T (Treg) cells are a subpopulation of T cells with the ability to control the responses of both CD4+ and CD8+ T cells. A case–control study was conducted in order to determine the functional attributes of Treg cells within the breast cancer milieu. Triple-color flow cytometry was utilized to study the phenotype expression of CD4+CD25+ Treg cells and CD8+ T cells in autologous tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) derived from 33 patients with stage I–III breast cancer. The prevalence of CD4+CD25+ T cells was significantly higher in TILs than in PBLs. The expressions of FOXP3 and GITR in CD4+CD25+ Treg cells were lower in PBLs than in TILs. Functional studies showed that both granzyme B and perforin were barely expressed in peripheral Treg cells but were highly expressed in Treg cells in the tumor microenvironment. On the contrary, down-regulation of both granzyme B and perforin expressed in the CD8+ cytotoxic T lymphocytes was significantly lower in TILs than in PBLs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules were synchronously up-regulated in CD8+ cytotoxic T cells. The in vitro kinetic study showed that adequate activation of TILs derived from breast cancer tissue could restore the appropriate antitumor immune response.
Literatur
1.
Zurück zum Zitat Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med. 2001;193:1285–94.PubMedCrossRef Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med. 2001;193:1285–94.PubMedCrossRef
2.
Zurück zum Zitat Standish LJ, Sweet ES, Novack J, Wenner CA, Bridge C, Nelson A, Martzen M, Torkelson C. Breast cancer and the immune system. J Soc Integr Oncol. 2008;6:158–68.PubMed Standish LJ, Sweet ES, Novack J, Wenner CA, Bridge C, Nelson A, Martzen M, Torkelson C. Breast cancer and the immune system. J Soc Integr Oncol. 2008;6:158–68.PubMed
3.
Zurück zum Zitat Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4+CD25 high Foxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res. 2007;13:4345–54.PubMedCrossRef Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4+CD25 high Foxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res. 2007;13:4345–54.PubMedCrossRef
4.
Zurück zum Zitat Kretschmer K, Apostolou I, Jaeckel E, Khazaie K, von Boehmer H. Making regulatory T cells with defined antigen specificity: role in autoimmunity and cancer. Immunol Rev. 2006;212:163–9.PubMedCrossRef Kretschmer K, Apostolou I, Jaeckel E, Khazaie K, von Boehmer H. Making regulatory T cells with defined antigen specificity: role in autoimmunity and cancer. Immunol Rev. 2006;212:163–9.PubMedCrossRef
5.
Zurück zum Zitat Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol. 2007;7:875–88.PubMedCrossRef Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol. 2007;7:875–88.PubMedCrossRef
6.
Zurück zum Zitat Gallimore A, Simon AK. Positive and negative influences of regulatory T cells on tumour immunity. Oncogene. 2008;27:5886–93.PubMedCrossRef Gallimore A, Simon AK. Positive and negative influences of regulatory T cells on tumour immunity. Oncogene. 2008;27:5886–93.PubMedCrossRef
7.
Zurück zum Zitat Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8:523–32.PubMedCrossRef Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8:523–32.PubMedCrossRef
8.
Zurück zum Zitat Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27:635–46.PubMedCrossRef Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27:635–46.PubMedCrossRef
9.
Zurück zum Zitat Siddiqui SA, Frigola X, Bonne-Annee S, Mercader M, Kuntz SM, Krambeck AE, Sengupta S, Dong H, Cheville JC, Lohse CM, et al. Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma. Clin Cancer Res. 2007;13:2075–81.PubMedCrossRef Siddiqui SA, Frigola X, Bonne-Annee S, Mercader M, Kuntz SM, Krambeck AE, Sengupta S, Dong H, Cheville JC, Lohse CM, et al. Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma. Clin Cancer Res. 2007;13:2075–81.PubMedCrossRef
10.
Zurück zum Zitat Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102:18538–43.PubMedCrossRef Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102:18538–43.PubMedCrossRef
11.
Zurück zum Zitat Jordanova ES, Gorter A, Ayachi O, Prins F, Durrant LG, Kenter GG, van der Burg SH, Fleuren GJ. Human leukocyte antigen class I, MHC class I chain-related molecule A and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res. 2008;14:2028–35.PubMedCrossRef Jordanova ES, Gorter A, Ayachi O, Prins F, Durrant LG, Kenter GG, van der Burg SH, Fleuren GJ. Human leukocyte antigen class I, MHC class I chain-related molecule A and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res. 2008;14:2028–35.PubMedCrossRef
12.
Zurück zum Zitat Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24:5373–80.PubMedCrossRef Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24:5373–80.PubMedCrossRef
13.
Zurück zum Zitat Viguier M, Lemaitre F, Verola O, Cho MS, Gorochov G, Dubertret L, Bachelez H, Kourilsky P, Ferradini L. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol. 2004;173:1444–53.PubMed Viguier M, Lemaitre F, Verola O, Cho MS, Gorochov G, Dubertret L, Bachelez H, Kourilsky P, Ferradini L. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol. 2004;173:1444–53.PubMed
14.
Zurück zum Zitat DeLong P, Carroll RG, Henry AC, Tanaka T, Ahmad S, Leibowitz MS, Sterman DH, June CH, Albelda SM, Vonderheide RH. Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma. Cancer Biol Ther. 2005;4:342–6.PubMedCrossRef DeLong P, Carroll RG, Henry AC, Tanaka T, Ahmad S, Leibowitz MS, Sterman DH, June CH, Albelda SM, Vonderheide RH. Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma. Cancer Biol Ther. 2005;4:342–6.PubMedCrossRef
15.
Zurück zum Zitat Sheu BC, Chiou SH, Lin HH, Chow SN, Huang SC, Ho HN, Hsu SM. Up-regulation of inhibitory natural killer receptors CD94/NKG2A with suppressed intracellular perforin expression of tumor-infiltrating CD8+ T lymphocytes in human cervical carcinoma. Cancer Res. 2005;65:2921–9.PubMedCrossRef Sheu BC, Chiou SH, Lin HH, Chow SN, Huang SC, Ho HN, Hsu SM. Up-regulation of inhibitory natural killer receptors CD94/NKG2A with suppressed intracellular perforin expression of tumor-infiltrating CD8+ T lymphocytes in human cervical carcinoma. Cancer Res. 2005;65:2921–9.PubMedCrossRef
16.
Zurück zum Zitat Sheu BC, Hsu SM, Ho HN, Lin RH, Torng PL, Huang SC. Reversed CD4/CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma. Cancer. 1999;86:1537–43.PubMedCrossRef Sheu BC, Hsu SM, Ho HN, Lin RH, Torng PL, Huang SC. Reversed CD4/CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma. Cancer. 1999;86:1537–43.PubMedCrossRef
17.
Zurück zum Zitat Sheu BC, Lin RH, Lien HC, Ho HN, Hsu SM, Huang SC. Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer. J Immunol. 2001;167:2972–8.PubMed Sheu BC, Lin RH, Lien HC, Ho HN, Hsu SM, Huang SC. Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer. J Immunol. 2001;167:2972–8.PubMed
18.
Zurück zum Zitat Sheu BC, Chang WC, Cheng CY, Lin HH, Chang DY, Huang SC. Cytokine regulation networks in the cancer microenvironment. Front Biosci. 2008;13:6255–68.PubMedCrossRef Sheu BC, Chang WC, Cheng CY, Lin HH, Chang DY, Huang SC. Cytokine regulation networks in the cancer microenvironment. Front Biosci. 2008;13:6255–68.PubMedCrossRef
19.
Zurück zum Zitat Sheu BC, Hsu SM, Ho HN, Lien HC, Huang SC, Lin RH. A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Res. 2001;61:237–42.PubMed Sheu BC, Hsu SM, Ho HN, Lien HC, Huang SC, Lin RH. A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Res. 2001;61:237–42.PubMed
20.
Zurück zum Zitat Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–61.PubMed Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–61.PubMed
21.
Zurück zum Zitat Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–61.PubMedCrossRef Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–61.PubMedCrossRef
22.
Zurück zum Zitat Huehn J, Siegmund K, Lehmann JC, Siewert C, Haubold U, Feuerer M, Debes GF, Lauber J, Frey O, Przybylski GK, et al. Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J Exp Med. 2004;199:303–13.PubMedCrossRef Huehn J, Siegmund K, Lehmann JC, Siewert C, Haubold U, Feuerer M, Debes GF, Lauber J, Frey O, Przybylski GK, et al. Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J Exp Med. 2004;199:303–13.PubMedCrossRef
23.
Zurück zum Zitat Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, Maeda M, Onodera M, Uchiyama T, Fujii S, et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol. 2004;16:1643–56.PubMedCrossRef Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, Maeda M, Onodera M, Uchiyama T, Fujii S, et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol. 2004;16:1643–56.PubMedCrossRef
24.
Zurück zum Zitat Kosmaczewska A, Ciszak L, Potoczek S, Frydecka I. The significance of Treg cells in defective tumor immunity. Arch Immunol Ther Exp (Warsz). 2008;56:181–91.CrossRef Kosmaczewska A, Ciszak L, Potoczek S, Frydecka I. The significance of Treg cells in defective tumor immunity. Arch Immunol Ther Exp (Warsz). 2008;56:181–91.CrossRef
25.
Zurück zum Zitat Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol. 2005;174:1783–6.PubMed Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol. 2005;174:1783–6.PubMed
26.
Zurück zum Zitat Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity. 2004;21:589–601.PubMedCrossRef Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity. 2004;21:589–601.PubMedCrossRef
27.
Zurück zum Zitat Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp Med. 2000;192:755–60.PubMedCrossRef Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp Med. 2000;192:755–60.PubMedCrossRef
28.
Zurück zum Zitat Chavez-Galan L, Arenas-Del Angel MC, Zenteno E, Chavez R, Lascurain R. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol. 2009;6:15–25.PubMedCrossRef Chavez-Galan L, Arenas-Del Angel MC, Zenteno E, Chavez R, Lascurain R. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol. 2009;6:15–25.PubMedCrossRef
29.
Zurück zum Zitat Trapani JA, Smyth MJ. Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol. 2002;2:735–47.PubMedCrossRef Trapani JA, Smyth MJ. Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol. 2002;2:735–47.PubMedCrossRef
30.
Zurück zum Zitat Medema JP, de Jong J, Peltenburg LT, Verdegaal EM, Gorter A, Bres SA, Franken KL, Hahne M, Albar JP, Melief CJ, et al. Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci USA. 2001;98:11515–20.PubMedCrossRef Medema JP, de Jong J, Peltenburg LT, Verdegaal EM, Gorter A, Bres SA, Franken KL, Hahne M, Albar JP, Melief CJ, et al. Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci USA. 2001;98:11515–20.PubMedCrossRef
31.
Zurück zum Zitat van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, Melief CJ, Zinkernagel RM, Hengartner H. Decreased tumor surveillance in perforin-deficient mice. J Exp Med. 1996;184:1781–90.PubMedCrossRef van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, Melief CJ, Zinkernagel RM, Hengartner H. Decreased tumor surveillance in perforin-deficient mice. J Exp Med. 1996;184:1781–90.PubMedCrossRef
32.
Zurück zum Zitat Street SE, Zerafa N, Iezzi M, Westwood JA, Stagg J, Musiani P, Smyth MJ. Host perforin reduces tumor number but does not increase survival in oncogene-driven mammary adenocarcinoma. Cancer Res. 2007;67:5454–60.PubMedCrossRef Street SE, Zerafa N, Iezzi M, Westwood JA, Stagg J, Musiani P, Smyth MJ. Host perforin reduces tumor number but does not increase survival in oncogene-driven mammary adenocarcinoma. Cancer Res. 2007;67:5454–60.PubMedCrossRef
33.
Zurück zum Zitat Waldner MJ, Wirtz S, Becker C, Seidel D, Tubbe I, Cappel K, Hahnel PS, Galle PR, Schuler M, Neurath MF. Perforin deficiency attenuates inflammation and tumor growth in colitis-associated cancer. Inflamm Bowel Dis. 2010;16:559–67.PubMed Waldner MJ, Wirtz S, Becker C, Seidel D, Tubbe I, Cappel K, Hahnel PS, Galle PR, Schuler M, Neurath MF. Perforin deficiency attenuates inflammation and tumor growth in colitis-associated cancer. Inflamm Bowel Dis. 2010;16:559–67.PubMed
34.
Zurück zum Zitat Chia J, Yeo KP, Whisstock JC, Dunstone MA, Trapani JA, Voskoboinik I. Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. Proc Natl Acad Sci USA. 2009;106:9809–14.PubMedCrossRef Chia J, Yeo KP, Whisstock JC, Dunstone MA, Trapani JA, Voskoboinik I. Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. Proc Natl Acad Sci USA. 2009;106:9809–14.PubMedCrossRef
35.
Zurück zum Zitat Radoja S, Saio M, Schaer D, Koneru M, Vukmanovic S, Frey AB. CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J Immunol. 2001;167:5042–51.PubMed Radoja S, Saio M, Schaer D, Koneru M, Vukmanovic S, Frey AB. CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J Immunol. 2001;167:5042–51.PubMed
36.
Zurück zum Zitat Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298:850–4.PubMedCrossRef Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298:850–4.PubMedCrossRef
37.
Zurück zum Zitat Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23:2346–57.PubMedCrossRef Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23:2346–57.PubMedCrossRef
38.
Zurück zum Zitat Gonzalo JA, Delaney T, Corcoran J, Goodearl A, Gutierrez-Ramos JC, Coyle AJ. Cutting edge: the related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T cell activation. J Immunol. 2001;166:1–5.PubMed Gonzalo JA, Delaney T, Corcoran J, Goodearl A, Gutierrez-Ramos JC, Coyle AJ. Cutting edge: the related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T cell activation. J Immunol. 2001;166:1–5.PubMed
39.
Zurück zum Zitat Demanet C, Brissinck J, De Jonge J, Thielemans K. Bispecific antibody-mediated immunotherapy of the BCL1 lymphoma: increased efficacy with multiple injections and CD28-induced costimulation. Blood. 1996;87:4390–8.PubMed Demanet C, Brissinck J, De Jonge J, Thielemans K. Bispecific antibody-mediated immunotherapy of the BCL1 lymphoma: increased efficacy with multiple injections and CD28-induced costimulation. Blood. 1996;87:4390–8.PubMed
40.
Zurück zum Zitat Viehl CT, Moore TT, Liyanage UK, Frey DM, Ehlers JP, Eberlein TJ, Goedegebuure PS, Linehan DC. Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice. Ann Surg Oncol. 2006;13:1252–8.PubMedCrossRef Viehl CT, Moore TT, Liyanage UK, Frey DM, Ehlers JP, Eberlein TJ, Goedegebuure PS, Linehan DC. Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice. Ann Surg Oncol. 2006;13:1252–8.PubMedCrossRef
Metadaten
Titel
Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer
verfasst von
Chao-Hsu Li
Wen-Hong Kuo
Wen-Chun Chang
Su-Cheng Huang
King-Jen Chang
Bor-Ching Sheu
Publikationsdatum
01.10.2011
Verlag
Humana Press Inc
Erschienen in
Immunologic Research / Ausgabe 1/2011
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-011-8242-x

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