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Published in: Journal of Translational Medicine 1/2014

Open Access 01-12-2014 | Research

Variability in CRP, regulatory T cells and effector T cells over time in gynaecological cancer patients: a study of potential oscillatory behaviour and correlations

Authors: Mutsa T Madondo, Sandra Tuyaerts, Brit B Turnbull, Anke Vanderstraeten, Holbrook Kohrt, Balasubramanian Narasimhan, Frederic Amant, Michael Quinn, Magdalena Plebanski

Published in: Journal of Translational Medicine | Issue 1/2014

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Abstract

Background

The inflammatory marker, C reactive protein has been proposed to also be a biomarker for adaptive immune responses in cancer patients with a possible application in time based chemotherapy. Fluxes in serum CRP levels were suggested to be indicative of a cyclical process in which, immune activation is followed by auto-regulating immune suppression. The applicability of CRP as a biomarker for regulatory or effector T cells was therefore investigated in a cohort of patients with gynaecological malignancies.

Methods

Peripheral blood samples were obtained from a cohort of patients at 7 time points over a period of 12 days. Serum and mononuclear cells were isolated and CRP levels in serum were detected using ELISA while regulatory and effector T cell frequencies were assessed using flow cytometry. To test periodicity, periodogram analysis of data was employed while Pearson correlation and the Wilcoxon signed rank test were used to determine correlations.

Results

The statistical analysis used showed no evidence of periodic oscillation in either serum CRP concentrations or Teff and Treg frequencies. Furthermore, there was no apparent correlation between serum CRP concentrations and the corresponding frequencies of Tregs or Teffs. Relative to healthy individuals, the disease state in the patients neither significantly affected the mean frequency of Tregs nor the mean coefficient of variation within the Treg population over time. However, both Teff mean frequency and mean coefficient of variation were significantly reduced in patients.

Conclusion

Using our methods we were unable to detect CRP oscillations that could be used as a consistent serial biomarker for time based chemotherapy.
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Literature
1.
go back to reference Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-674. 10.1016/j.cell.2011.02.013.CrossRefPubMed Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-674. 10.1016/j.cell.2011.02.013.CrossRefPubMed
2.
go back to reference Maccio A, Madeddu C: Inflammation and ovarian cancer. Cytokine. 2012, 58: 133-147. 10.1016/j.cyto.2012.01.015.CrossRefPubMed Maccio A, Madeddu C: Inflammation and ovarian cancer. Cytokine. 2012, 58: 133-147. 10.1016/j.cyto.2012.01.015.CrossRefPubMed
3.
go back to reference Wallace AE, Gibson DA, Saunders PT, Jabbour HN: Inflammatory events in endometrial adenocarcinoma. J Endocrinol. 2010, 206: 141-157. 10.1677/JOE-10-0072.CrossRefPubMed Wallace AE, Gibson DA, Saunders PT, Jabbour HN: Inflammatory events in endometrial adenocarcinoma. J Endocrinol. 2010, 206: 141-157. 10.1677/JOE-10-0072.CrossRefPubMed
4.
go back to reference Brannstrom M, Pascoe V, Norman RJ, McClure N: Localization of leukocyte subsets in the follicle wall and in the corpus luteum throughout the human menstrual cycle. Fertil Steril. 1994, 61: 488-495.PubMed Brannstrom M, Pascoe V, Norman RJ, McClure N: Localization of leukocyte subsets in the follicle wall and in the corpus luteum throughout the human menstrual cycle. Fertil Steril. 1994, 61: 488-495.PubMed
5.
go back to reference Dahm-Kahler P, Ghahremani M, Lind AK, Sundfeldt K, Brannstrom M: Monocyte chemotactic protein-1 (MCP-1), its receptor, and macrophages in the perifollicular stroma during the human ovulatory process. Fertil Steril. 2009, 91: 231-239. 10.1016/j.fertnstert.2007.07.1330.CrossRefPubMed Dahm-Kahler P, Ghahremani M, Lind AK, Sundfeldt K, Brannstrom M: Monocyte chemotactic protein-1 (MCP-1), its receptor, and macrophages in the perifollicular stroma during the human ovulatory process. Fertil Steril. 2009, 91: 231-239. 10.1016/j.fertnstert.2007.07.1330.CrossRefPubMed
6.
go back to reference He YY, Cai B, Yang YX, Liu XL, Wan XP: Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci. 2009, 100: 1051-1061. 10.1111/j.1349-7006.2009.01148.x.CrossRefPubMed He YY, Cai B, Yang YX, Liu XL, Wan XP: Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci. 2009, 100: 1051-1061. 10.1111/j.1349-7006.2009.01148.x.CrossRefPubMed
7.
go back to reference Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, Balkwill FR, Hagemann T: The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest. 2009, 119: 3011-3023. 10.1172/JCI39065.PubMedCentralCrossRefPubMed Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, Balkwill FR, Hagemann T: The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest. 2009, 119: 3011-3023. 10.1172/JCI39065.PubMedCentralCrossRefPubMed
8.
go back to reference Kulbe H, Chakravarty P, Leinster DA, Charles KA, Kwong J, Thompson RG, Coward JI, Schioppa T, Robinson SC, Gallagher WM, Galletta L, Salako MA, Smyth JF, Hagemann T, Brennan DJ, Bowtell DD, Balkwill FR, Australian Ovarian Cancer Study Group: A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Res. 2012, 72: 66-75.PubMedCentralCrossRefPubMed Kulbe H, Chakravarty P, Leinster DA, Charles KA, Kwong J, Thompson RG, Coward JI, Schioppa T, Robinson SC, Gallagher WM, Galletta L, Salako MA, Smyth JF, Hagemann T, Brennan DJ, Bowtell DD, Balkwill FR, Australian Ovarian Cancer Study Group: A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Res. 2012, 72: 66-75.PubMedCentralCrossRefPubMed
9.
go back to reference Burke F, Relf M, Negus R, Balkwill F: A cytokine profile of normal and malignant ovary. Cytokine. 1996, 8: 578-585. 10.1006/cyto.1996.0077.CrossRefPubMed Burke F, Relf M, Negus R, Balkwill F: A cytokine profile of normal and malignant ovary. Cytokine. 1996, 8: 578-585. 10.1006/cyto.1996.0077.CrossRefPubMed
10.
go back to reference Rabinovich A, Medina L, Piura B, Segal S, Huleihel M: Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6. Anticancer Res. 2007, 27: 267-272.PubMed Rabinovich A, Medina L, Piura B, Segal S, Huleihel M: Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6. Anticancer Res. 2007, 27: 267-272.PubMed
11.
go back to reference Young DP, Kushner I, Samols D: Binding of C/EBPbeta to the C-reactive protein (CRP) promoter in Hep3B cells is associated with transcription of CRP mRNA. J Immunol. 2008, 181: 2420-2427. 10.4049/jimmunol.181.4.2420.CrossRefPubMed Young DP, Kushner I, Samols D: Binding of C/EBPbeta to the C-reactive protein (CRP) promoter in Hep3B cells is associated with transcription of CRP mRNA. J Immunol. 2008, 181: 2420-2427. 10.4049/jimmunol.181.4.2420.CrossRefPubMed
12.
go back to reference Yoshizaki K: Pathogenic role of IL-6 combined with TNF-alpha or IL-1 in the induction of acute phase proteins SAA and CRP in chronic inflammatory diseases. Adv Exp Med Biol. 2011, 691: 141-150. 10.1007/978-1-4419-6612-4_15.CrossRefPubMed Yoshizaki K: Pathogenic role of IL-6 combined with TNF-alpha or IL-1 in the induction of acute phase proteins SAA and CRP in chronic inflammatory diseases. Adv Exp Med Biol. 2011, 691: 141-150. 10.1007/978-1-4419-6612-4_15.CrossRefPubMed
13.
go back to reference Coventry BJ, Ashdown ML, Quinn MA, Markovic SN, Yatomi-Clarke SL, Robinson AP: CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?. J Transl Med. 2009, 7: 102-10.1186/1479-5876-7-102.PubMedCentralCrossRefPubMed Coventry BJ, Ashdown ML, Quinn MA, Markovic SN, Yatomi-Clarke SL, Robinson AP: CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?. J Transl Med. 2009, 7: 102-10.1186/1479-5876-7-102.PubMedCentralCrossRefPubMed
14.
go back to reference Li J, Mo HY, Xiong G, Zhang L, He J, Huang ZF, Liu ZW, Chen QY, Du ZM, Zheng LM, Qian CN, Zeng YX: Tumor microenvironment MIF directs the accumulation of IL-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. J Biol Chem. 2012, 287: 35484-35495. 10.1074/jbc.M112.367532.PubMedCentralCrossRefPubMed Li J, Mo HY, Xiong G, Zhang L, He J, Huang ZF, Liu ZW, Chen QY, Du ZM, Zheng LM, Qian CN, Zeng YX: Tumor microenvironment MIF directs the accumulation of IL-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. J Biol Chem. 2012, 287: 35484-35495. 10.1074/jbc.M112.367532.PubMedCentralCrossRefPubMed
15.
go back to reference Katz SC, Bamboat ZM, Maker AV, Shia J, Pillarisetty VG, Yopp AC, Hedvat CV, Gonen M, Jarnagin WR, Fong Y, D’Angelica MI, DeMatteo RP: Regulatory T Cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2013, 20: 946-955. 10.1245/s10434-012-2668-9.PubMedCentralCrossRefPubMed Katz SC, Bamboat ZM, Maker AV, Shia J, Pillarisetty VG, Yopp AC, Hedvat CV, Gonen M, Jarnagin WR, Fong Y, D’Angelica MI, DeMatteo RP: Regulatory T Cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2013, 20: 946-955. 10.1245/s10434-012-2668-9.PubMedCentralCrossRefPubMed
16.
go back to reference Allan SE, Crome SQ, Crellin NK, Passerini L, Steiner TS, Bacchetta R, Roncarolo MG, Levings MK: Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol. 2007, 19: 345-354. 10.1093/intimm/dxm014.CrossRefPubMed Allan SE, Crome SQ, Crellin NK, Passerini L, Steiner TS, Bacchetta R, Roncarolo MG, Levings MK: Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol. 2007, 19: 345-354. 10.1093/intimm/dxm014.CrossRefPubMed
17.
go back to reference Miller AM, Lundberg K, Ozenci V, Banham AH, Hellstrom M, Egevad L, Pisa P: CD4 + CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol. 2006, 177: 7398-7405. 10.4049/jimmunol.177.10.7398.CrossRefPubMed Miller AM, Lundberg K, Ozenci V, Banham AH, Hellstrom M, Egevad L, Pisa P: CD4 + CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol. 2006, 177: 7398-7405. 10.4049/jimmunol.177.10.7398.CrossRefPubMed
18.
go back to reference Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W: Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004, 10: 942-949. 10.1038/nm1093.CrossRefPubMed Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W: Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004, 10: 942-949. 10.1038/nm1093.CrossRefPubMed
19.
go back to reference Hamano R, Huang J, Yoshimura T, Oppenheim JJ, Chen X: TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40. Eur J Immunol. 2011, 41: 2010-2020. 10.1002/eji.201041205.PubMedCentralCrossRefPubMed Hamano R, Huang J, Yoshimura T, Oppenheim JJ, Chen X: TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40. Eur J Immunol. 2011, 41: 2010-2020. 10.1002/eji.201041205.PubMedCentralCrossRefPubMed
20.
go back to reference Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A, Fazekas de St Groth B, Kelleher A, Fazekas-de-St-Groth B: Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med. 2006, 203: 1693-1700. 10.1084/jem.20060468.PubMedCentralCrossRefPubMed Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A, Fazekas de St Groth B, Kelleher A, Fazekas-de-St-Groth B: Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med. 2006, 203: 1693-1700. 10.1084/jem.20060468.PubMedCentralCrossRefPubMed
21.
go back to reference Triplett TA, Curti BD, Bonafede PR, Miller WL, Walker EB, Weinberg AD: Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3NEG. Eur J Immunol. 2012, 42: 1893-1905. 10.1002/eji.201242444.CrossRefPubMed Triplett TA, Curti BD, Bonafede PR, Miller WL, Walker EB, Weinberg AD: Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3NEG. Eur J Immunol. 2012, 42: 1893-1905. 10.1002/eji.201242444.CrossRefPubMed
22.
go back to reference Bollinger T, Leutz A, Leliavski A, Skrum L, Kovac J, Bonacina L, Benedict C, Lange T, Westermann J, Oster H, Solbach W: Circadian clocks in mouse and human CD4+ T cells. PLoS One. 2011, 6: e29801-10.1371/journal.pone.0029801.PubMedCentralCrossRefPubMed Bollinger T, Leutz A, Leliavski A, Skrum L, Kovac J, Bonacina L, Benedict C, Lange T, Westermann J, Oster H, Solbach W: Circadian clocks in mouse and human CD4+ T cells. PLoS One. 2011, 6: e29801-10.1371/journal.pone.0029801.PubMedCentralCrossRefPubMed
23.
go back to reference Mustea A, Konsgen D, Braicu EI, Pirvulescu C, Sun P, Sofroni D, Lichtenegger W, Sehouli J: Expression of IL-10 in patients with ovarian carcinoma. Anticancer Res. 2006, 26: 1715-1718.PubMed Mustea A, Konsgen D, Braicu EI, Pirvulescu C, Sun P, Sofroni D, Lichtenegger W, Sehouli J: Expression of IL-10 in patients with ovarian carcinoma. Anticancer Res. 2006, 26: 1715-1718.PubMed
24.
go back to reference Hirashima Y, Kobayashi H, Suzuki M, Tanaka Y, Kanayama N, Terao T: Transforming growth factor-beta1 produced by ovarian cancer cell line HRA stimulates attachment and invasion through an up-regulation of plasminogen activator inhibitor type-1 in human peritoneal mesothelial cells. J Biol Chem. 2003, 278: 26793-26802. 10.1074/jbc.M212187200.CrossRefPubMed Hirashima Y, Kobayashi H, Suzuki M, Tanaka Y, Kanayama N, Terao T: Transforming growth factor-beta1 produced by ovarian cancer cell line HRA stimulates attachment and invasion through an up-regulation of plasminogen activator inhibitor type-1 in human peritoneal mesothelial cells. J Biol Chem. 2003, 278: 26793-26802. 10.1074/jbc.M212187200.CrossRefPubMed
25.
go back to reference Lechner MG, Megiel C, Russell SM, Bingham B, Arger N, Woo T, Epstein AL: Functional characterization of human Cd33+ and Cd11b + myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines. J Transl Med. 2011, 9: 90-10.1186/1479-5876-9-90.PubMedCentralCrossRefPubMed Lechner MG, Megiel C, Russell SM, Bingham B, Arger N, Woo T, Epstein AL: Functional characterization of human Cd33+ and Cd11b + myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines. J Transl Med. 2011, 9: 90-10.1186/1479-5876-9-90.PubMedCentralCrossRefPubMed
26.
go back to reference Leontovich AA, Dronca RS, Suman VJ, Ashdown ML, Nevala WK, Thompson MA, Robinson A, Kottschade LA, Kaur JS, McWilliams RR, Ivanov LV, Croghan GA, Markovic SN: Fluctuation of systemic immunity in melanoma and implications for timing of therapy. Front Biosci (Elite Ed). 2012, 4: 958-975.CrossRef Leontovich AA, Dronca RS, Suman VJ, Ashdown ML, Nevala WK, Thompson MA, Robinson A, Kottschade LA, Kaur JS, McWilliams RR, Ivanov LV, Croghan GA, Markovic SN: Fluctuation of systemic immunity in melanoma and implications for timing of therapy. Front Biosci (Elite Ed). 2012, 4: 958-975.CrossRef
27.
go back to reference French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR: Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. J Clin Endocrinol Metab. 2010, 95: 2325-2333. 10.1210/jc.2009-2564.PubMedCentralCrossRefPubMed French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR: Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. J Clin Endocrinol Metab. 2010, 95: 2325-2333. 10.1210/jc.2009-2564.PubMedCentralCrossRefPubMed
28.
go back to reference Ostrand-Rosenberg S, Sinha P: Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol. 2009, 182: 4499-4506. 10.4049/jimmunol.0802740.PubMedCentralCrossRefPubMed Ostrand-Rosenberg S, Sinha P: Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol. 2009, 182: 4499-4506. 10.4049/jimmunol.0802740.PubMedCentralCrossRefPubMed
29.
go back to reference Park HJ, Kusnadi A, Lee EJ, Kim WW, Cho BC, Lee IJ, Seong J, Ha SJ: Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors. Cell Immunol. 2012, 278: 76-83. 10.1016/j.cellimm.2012.07.001.CrossRefPubMed Park HJ, Kusnadi A, Lee EJ, Kim WW, Cho BC, Lee IJ, Seong J, Ha SJ: Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors. Cell Immunol. 2012, 278: 76-83. 10.1016/j.cellimm.2012.07.001.CrossRefPubMed
30.
go back to reference Schuler PJ, Schilling B, Harasymczuk M, Hoffmann TK, Johnson J, Lang S, Whiteside TL: Phenotypic and functional characteristics of CD4+ CD39+ FOXP3+ and CD4+ CD39+ FOXP3neg T-cell subsets in cancer patients. Eur J Immunol. 2012, 42: 1876-1885. 10.1002/eji.201142347.PubMedCentralCrossRefPubMed Schuler PJ, Schilling B, Harasymczuk M, Hoffmann TK, Johnson J, Lang S, Whiteside TL: Phenotypic and functional characteristics of CD4+ CD39+ FOXP3+ and CD4+ CD39+ FOXP3neg T-cell subsets in cancer patients. Eur J Immunol. 2012, 42: 1876-1885. 10.1002/eji.201142347.PubMedCentralCrossRefPubMed
31.
go back to reference Chen ZF, Xu Q, Ding JB, Zhang Y, Du R, Ding Y: CD4 + CD25 + Foxp3+ Treg and TGF-beta play important roles in pathogenesis of Uygur cervical carcinoma. Eur J Gynaecol Oncol. 2012, 33: 502-507.PubMed Chen ZF, Xu Q, Ding JB, Zhang Y, Du R, Ding Y: CD4 + CD25 + Foxp3+ Treg and TGF-beta play important roles in pathogenesis of Uygur cervical carcinoma. Eur J Gynaecol Oncol. 2012, 33: 502-507.PubMed
32.
go back to reference Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M: Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012, 13: 832-842. 10.1038/ni.2376.PubMedCentralCrossRefPubMed Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M: Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012, 13: 832-842. 10.1038/ni.2376.PubMedCentralCrossRefPubMed
33.
go back to reference Nunez S, Saez JJ, Fernandez D, Flores-Santibanez F, Alvarez K, Tejon G, Ruiz P, Maldonado P, Hidalgo Y, Manriquez V, Bono MR, Rosemblatt M, Sauma D: Th17 cells contribute to anti-tumor immunity and promote the recruitment of th1 cells to the tumor. Immunology. 2013, 139: 61-71. 10.1111/imm.12055.PubMedCentralCrossRefPubMed Nunez S, Saez JJ, Fernandez D, Flores-Santibanez F, Alvarez K, Tejon G, Ruiz P, Maldonado P, Hidalgo Y, Manriquez V, Bono MR, Rosemblatt M, Sauma D: Th17 cells contribute to anti-tumor immunity and promote the recruitment of th1 cells to the tumor. Immunology. 2013, 139: 61-71. 10.1111/imm.12055.PubMedCentralCrossRefPubMed
34.
go back to reference Gao Y, Whitaker-Dowling P, Griffin JA, Bergman I: Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells. Cancer Gene Ther. 2012, 19: 282-291. 10.1038/cgt.2011.90.PubMedCentralCrossRefPubMed Gao Y, Whitaker-Dowling P, Griffin JA, Bergman I: Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells. Cancer Gene Ther. 2012, 19: 282-291. 10.1038/cgt.2011.90.PubMedCentralCrossRefPubMed
35.
go back to reference Quezada SA, Simpson TR, Peggs KS, Merghoub T, Vider J, Fan X, Blasberg R, Yagita H, Muranski P, Antony PA, Restifo NP, Allison JP: Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med. 2010, 207: 637-650. 10.1084/jem.20091918.PubMedCentralCrossRefPubMed Quezada SA, Simpson TR, Peggs KS, Merghoub T, Vider J, Fan X, Blasberg R, Yagita H, Muranski P, Antony PA, Restifo NP, Allison JP: Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med. 2010, 207: 637-650. 10.1084/jem.20091918.PubMedCentralCrossRefPubMed
Metadata
Title
Variability in CRP, regulatory T cells and effector T cells over time in gynaecological cancer patients: a study of potential oscillatory behaviour and correlations
Authors
Mutsa T Madondo
Sandra Tuyaerts
Brit B Turnbull
Anke Vanderstraeten
Holbrook Kohrt
Balasubramanian Narasimhan
Frederic Amant
Michael Quinn
Magdalena Plebanski
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-12-179

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