Abstract
Cytokines are low molecular weight regulatory proteins or glycoprotein that modulates the intensity and duration of immune response by stimulating or inhibiting the activation, proliferation, and/or differentiation of target cells. Different cytokines are known to have diverse role in breast cancer initiation and progression. Interleukin-10 (IL-10), a pleiotropic anti-inflammatory cytokine, induces immunosuppression and assists in escape from tumor immune surveillance. Like several other cytokines, IL-10 also can exert dual proliferative and inhibitory effect on breast tumor cells indicating a complex role of IL-10 in breast cancer initiation and progression. In this review, we tried to put together a comprehensive current view on significance of IL-10 in promotion, inhibition, and importance as prognosticator in breast cancer based on in vitro, in vivo, and clinical evidences. For literature collection, we conducted PubMed search with keywords “IL-10” and “breast cancer”.
Similar content being viewed by others
References
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
Parkin DM, Fernandez LM (2006) Use of statistics to assess the global burden of breast cancer. Breast J 12(Suppl. 1):70–80
Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y (2004) Cytokines in cancer immunity and immunotherapy. Immunol Rev 202:275–293
Standish LJ, Sweet ES, Novack J, Wenner CA, Bridge C, Nelson A, Martzen M, Torkelson C (2008) Breast cancer and the immune system. J Soc Integr Oncol 6(4):158–168
DeNardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9(4):212
Rao VS, Dyer CE, Jameel JK, Drew PJ, Greenman J (2006) Potential prognostic and therapeutic roles for cytokines in breast cancer (Review). Oncol Rep 15(1):179–185
Carpi A, Nicolini A, Antonelli A, Ferrari P, Rossi G (2009) Cytokines in the management of high risk or advanced breast cancer: an update and expectation. Curr Cancer Drug Target 9(8):888–903
Konwar R, Chaudhary P, Kumar S, Mishra D, Chattopadhyay N, Bid HK (2009) Breast cancer risk associated with polymorphisms of IL-1RN and IL-4 gene in Indian women. Oncol Res 17(8):367–372
Moore KW, O’Garra A, de Waal MR, Vieira P, Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190
Fitzgerald KA, O’Neill LAJ, Gearing AJH, Callard RE (2001) The cytokine facts book, 2nd edn. Academic Press, London
Lentsch AB, Shanley TP, Sarma V, Ward PA (1997) In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13. J Clin Invest 100(10):2443–2448
Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S (1997) Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J 16(19):5894–5903
Mosmann TR (1994) Properties and functions of interleukin-10. Adv Immunol 56:1–26
Howard M, O’Garra A (1992) Biological properties of interleukin 10. Immunol Today 13(6):198–200
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765
Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22:929–979
Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29:71–109
de Waal Malefyt R, Yssel H, Roncarolo MG, Spits H, de Vries JE (1992) Interleukin-10. Curr Opin Immunol 4(3):314–320
Asadullah K, Sterry W, Volk HD (2003) Interleukin-10 therapy—review of a new approach. Pharmacol Rev 55(2):241–269
Sabat R, Grütz G, Warszawska K, Kirsch S, Witte E, Wolk K, Geginat J (2010) Biology of interleukin-10. Cytokine Growth Factor Rev 21(5):331–344
Wolk K, Kunz S, Asadullah K, Sabat R (2002) Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol 168(11):5397–5402
Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771–5777
O’Garra A, Vieira P (2007) TH1 cells control themselves by producing interleukin-10. Nat Rev Immunol 7:425–428
Ho AS, Wei SH, Mui AL, Miyajima A, Moore KW (1995) Functional regions of the mouse interleukin-10 receptor cytoplasmic domain. Mol Cell Biol 15:5043–5053
Finbloom DS, Winestock KD (1995) IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol 155(3):1079–1090
Lai CF, Ripperger J, Morella KK, Jurlander J, Hawley TS, Carson WE, Kordula T, Caligiuri MA, Hawley RG, Fey GH, Baumann H (1996) Receptors for interleukin (IL)-10 and IL-6-type cytokines use similar signaling mechanisms for inducing transcription through IL-6 response elements. J Biol Chem 271(24):13968–13975
Williams LM, Ricchetti G, Sarma U, Smallie T, Foxwell BM (2004) Interleukin-10 suppression of myeloid cell activation—a continuing puzzle. Immunology 113(3):281–292
Braunschweig A, Poehlmann TG, Busch S, Schleussner E, Markert UR (2011) Signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling (SOCS3) balance controls cytotoxicity and IL-10 expression in decidual-like natural killer cell line NK-92. Am J Reprod Immunol 66(3):329–335
Lee EB, Kim A, Kang K, Kim H, Lim JS (2010) NDRG2-mediated modulation of SOCS3 and STAT3 activity inhibits IL-10 production. Immune Netw 10(6):219–229
Haddad JJ, Saadé NE, Safieh-Garabedian B (2003) Interleukin-10 and the regulation of mitogen-activated protein kinases: are these signalling modules targets for the anti-inflammatory action of this cytokine? Cell Signal 15(3):255–267
Kruger-Krasagakes S, Krasagakis K, Garbe C, Schmitt E, Hüls C, Blankenstein T, Diamantstein T (1994) Expression of interleukin 10 in human melanoma. Br J Cancer 70(6):1182–1185
Gastl GA, Abrams JS, Nanus DM, Oosterkamp R, Silver J, Liu F, Chen M, Albino AP, Bander NH (1993) Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin-6 expression. Int J Cancer 55(1):96–101
Joimel U, Gest C, Soria J, Pritchard LL, Alexandre J, Laurent M, Blot E, Cazin L, Vannier JP, Varin R et al (2010) Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate. BMC Cancer 10:375
Venetsanakos E, Beckman I, Bradley J, Skinner JM (1997) High incidence of interleukin 10 mRNA but not interleukin 2 mRNA detected in human breast tumours. Br J Cancer 75(12):1826–1830
Al-Sarireh B, Sathaporn S, Robins A, Jenkin D, Vassanasiri W, El-Sheemy M, Jibril JA, Clark D, Eremin O (2010) Mononuclear phagocytes but not tumour cells are the main source of elevated inter-leukin (IL)-10 levels in human breast cancer. Surgeons in training 2000. The Royal College of Surgeons of Edinburgh. Retrieved on 02 December 2010 from http://www.rcsed.ac.uk/Journal/vol46_1/4610011.htm
Bogdan C, Vodovotz Y, Nathan C (1991) Macrophage deactivation by interleukin 10. J Exp Med 174(6):1549–1555
Hashimoto SI, Komuro I, Yamada M, Akagawa KS (2001) IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages. J Immunol 167(7):3619–3625
Commeren DL, Van Soest PL, Karimi K, Löwenberg B, Cornelissen JJ, Braakman E (2003) Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells. Immunology 110(2):188–196
de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174(4):915–924
Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A (1991) IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 146(10):3444–3451
Macatonia SE, Doherty TM, Knight SC, O’Garra A (1993) Differential effect of IL-10 on dendritic cell-induced T cell proliferation and IFN-gamma production. J Immunol 150(9):3755–3765
de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE (1991) Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174(5):1209–1220
Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A (1991) IL-10 inhibits cytokine production by activated macrophages. J Immunol 147(11):3815–3822
Jenkins JK, Malyak M, Arend WP (1994) The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils. Lymphokine Cytokine Res 13(1):47–54
Huber S, Gagliani N, Esplugues E, O’Connor W Jr, Huber FJ, Chaudhry A, Kamanaka M, Kobayashi Y, Booth CJ, Rudensky AY et al (2011) Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. Immunity 34(4):554–565
Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich JM, Jack RS, Wunderlich FT, Brüning JC, Müller W et al (2011) Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 34(4):566–578
Scott DE, Gause WC, Finkelman FD, Steinberg AD (1990) Anti-CD3 antibody induces rapid expression of cytokine genes in vivo. J Immunol 145(7):2183–2188
Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, Francis JN, Durham SR (2007) Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. J Immunol 178(7):4658–4666
Geissmann F, Launay P, Pasquier B, Lepelletier Y, Leborgne M, Lehuen A, Brousse N, Monteiro RC (2001) A subset of human dendritic cells expresses IgA Fc receptor (CD89), which mediates internalization and activation upon cross-linking by IgA complexes. J Immunol 166(1):346–352
McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8(12):1390–1397
Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL (2007) A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8(12):1380–1389
Fitzgerald DC, Zhang GX, El-Behi M, Fonseca-Kelly Z, Li H, Yu S, Saris CJ, Gran B, Ciric B, Rostami A (2007) Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 8(12):1372–1379
Pang G, Couch L, Batey R, Clancy R, Cripps A (1994) GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-alpha. Clin Exp Immunol 96(3):437–443
Kim KH, Kim DI, Kim SH, Jung EM, Kang JH, Jeung EB, Yang MP (2011) Trans-10, cis-12-conjugated linoleic acid attenuates tumor necrosis factor-α production by lipopolysaccharide-stimulated porcine peripheral blood mononuclear cells through induction of interleukin-10. Cytokine; doi:10.1016/j.cyto.2011.06.019
Brunsing RL, Prossnitz ER (2011) Induction of interleukin-10 in the T helper type 17 effector population by the G protein coupled estrogen receptor (GPER) agonist G-1. Immunology 134(1):93–106
Lazarini M, Traina F, Winnischofer SM, Costa FF, Queiroz ML, Saad ST (2011) Effects of thalidomide on long-term bone marrow cultures from patients with myelodysplastic syndromes: induction of IL-10 expression in the stromal layers. Leuk Res 35(8):1102–1107
Lian ZR, Xu YF, Wang XB, Gong JP, Liu ZJ (2011) Suppression of Histone Deacetylase 11 Promotes Expression of IL-10 in Kupffer Cells and Induces Tolerance Following Orthotopic Liver Transplantation in Rats. J Surg Res; doi:10.1016/j.jss.2010.12.035
Municio C, Hugo E, Alvarez Y, Alonso S, Blanco L, Fernández N, Sánchez Crespo M (2011) Apoptotic cells enhance IL-10 and reduce IL-23 production in human dendritic cells treated with zymosan. Mol Immunol; doi:10.1016/j.molimm.2011.07.022
Xu J, Yang Y, Qiu G, Lal G, Wu Z, Levy DE, Ochando JC, Bromberg JS, Ding Y (2009) c-Maf regulates IL-10 expression during Th17 polarization. J Immunol 182(10):6226–6236
Durez P, Abramowicz D, Gérard C, Van Mechelen M, Amraoui Z, Dubois C, Leo O, Velu T, Goldman M (1993) In vivo induction of interleukin 10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A. J Exp Med 177(2):551–555
Ji JD, Kim HJ, Rho YH, Choi SJ, Lee YH, Cheon HJ, Sohn J, Song GG (2005) Inhibition of IL-10-induced STAT3 activation by 15-deoxy-Delta12, 14-prostaglandin J2. Rheumatology (Oxford) 44(8):983–988
Kalechman Y, Gafter U, Weinstein T, Chagnac A, Freidkin I, Tobar A, Albeck M, Sredni B (2004) Inhibition of interleukin-10 by the immunomodulator AS101 reduces mesangial cell proliferation in experimental mesangioproliferative glomerulonephritis: association with dephosphorylation of STAT3. J Biol Chem 279(23):24724–24732
Alas S, Emmanouilides C, Bonavida B (2001) Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin’s lymphoma to apoptosis. Clin Cancer Res 7(3):709–723
Kundu N, Beaty TL, Jackson MJ, Fulton AM (1996) Antimetastatic and antitumor activities of interleukin 10 in a murine model of breast cancer. J Natl Cancer Inst 88(8):536–541
Mocellin S, Marincola FM, Young HA (2005) Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 78(5):1043–1051
Pinzon-Charry A, Maxwell T, López JA (2005) Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol Cell Biol 83(5):451–461
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674
Cohen SB, Crawley JB, Kahan MC, Feldmann M, Foxwell BM (1997) Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2. Immunology 92:1–5
Taga K, Cherney B, Tosato G (1993) IL-10 inhibits apoptotic cell death in human T cells starved of IL-2. Int Immunol 5:1599–1608
Alas S, Bonavida B (2001) Rituximab inactivates signal transducer and activation of transcription 3 (stat3) activity in b-nonhodgkin’s lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of bcl-2 and sensitization to cytotoxic drugs. Cancer Res 61:5137–5144
Wang XZ, Zhang SJ, Chen YX, Chen ZX, Huang YH, Zhang LJ (2004) Effects of platelet-derived growth factor and interleukin-10 on Fas/Fas-ligand and Bcl-2/Bax mRNA expression in rat hepatic stellate cells in vitro. World J Gastroenterol 10:2706–2710
Zeng L, O’Connor C, Zhang J, Kaplan AM, Cohen DA (2010) IL-10 promotes resistance to apoptosis and metastatic potential in lung tumor cell lines. Cytokine 49(3):294–302
Fox JG, Sheppard BJ, Dangler CA, Whary MT, Ihrig M, Wang TC (2002) Germ-line p53-targeted disruption inhibits helicobacter induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses. Cancer Res 62:696–702
Okuda Y, Okuda M, Bernard CC (2003) Regulatory role of p53 in experimental autoimmune encephalomyelitis. J Neuroimmunol 135:29–37
Ohkuso-Tsukada K, Tsukada T, Isobe KI (1999) Accelerated development and aging of the immune system in p53-deficient mice. J Immunol 163:1966–1972
Kohno T, Mizukami H, Suzuki M, Saga Y, Takei Y, Shimpo M, Matsushita T, Okada T, Hanazono Y, Kume A, Sato I, Ozawa K (2003) Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VEGF-producing ovarian cancer. Cancer Res 63(16):5091–5094
Stearns ME, Rhim J, Wang M (1999) Interleukin 10 (IL-10) inhibition of primary human prostate cell-induced angiogenesis: IL-10 stimulation of tissue inhibitor of metalloproteinase-1 and inhibition of matrix metalloproteinase (MMP)-2/MMP-9 secretion. Clin Cancer Res 5(1):189–196
García-Hernández ML, Hernández-Pando R, Gariglio P, Berumen J (2002) Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation. Immunology 105(2):231–243
Huang S, Xie K, Bucana CD, Ullrich SE, Bar-Eli M (1996) Interleukin 10 suppresses tumor growth and metastasis of human melanoma cells: potential inhibition of angiogenesis. Clin Cancer Res 2(12):1969–1979
Fujii S, Shimizu K, Shimizu T, Lotze MT (2001) Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood 98(7):2143–2151
Segal BM, Glass DD, Shevach EM (2002) Cutting edge: IL-10-producing CD4+ T cells mediate tumor rejection. J Immunol 168(1):1–4
Garcia-Lora A, Algarra I, Garrido F (2003) MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol 195(3):346–355
Di Carlo E, Coletti A, Modesti A, Giovarelli M, Forni G, Musiani P (1998) Local release of interleukin-10 by transfected mouse adenocarcinoma cells exhibits pro- and anti-inflammatory activity and results in a delayed tumor rejection. Eur Cytokine Netw 9(1):61–68
Kaufman HL, Rao JB, Irvine KR, Bronte V, Rosenberg SA, Restifo NP (1999) Interleukin-10 enhances the therapeutic effectiveness of a recombinant poxvirus-based vaccine in an experimental murine tumor model. J Immunother 22(6):489–496
Dorsey R, Kundu N, Yang Q, Tannenbaum CS, Sun H, Hamilton TA, Fulton AM (2002) Immunotherapy with interleukin-10 depends on the CXC chemokines inducible protein-10 and monokine induced by IFN-gamma. Cancer Res 62(9):2606–2610
Allione A, Consalvo M, Nanni P, Lollini PL, Cavallo F, Giovarelli M, Forni M, Gulino A, Colombo MP, Dellabona P et al (1994) Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants. Cancer Res 54(23):6022–6026
Giovarelli M, Musiani P, Modesti A, Dellabona P, Casorati G, Allione A, Consalvo M, Cavallo F, di Pierro F, De Giovanni C (1995) Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory. J Immunol 155(6):3112–3123
Kundu N, Dorsey R, Jackson MJ, Guiterrez P, Wilson K, Fu S, Ramanujam K, Thomas E, Fulton AM (1998) Interleukin-10 gene transfer inhibits murine mammary tumors and elevates nitric oxide. Int J Cancer 76(5):713–719
Paul S, Biswas A, Sasmal K, Mukherjee S, Biswas T, Biswas R (2010) IL-10 alters prolactin receptor activity emulating that during breast cancer. Cytokine 51(2):144–150
Halak BK, Maguire HC Jr, Lattime EC (1999) Tumor-induced interleukin-10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site. Cancer Res 59(4):911–917
Abbas AK, Lichtman AH (2006) Cellular and molecular immunology, 5th edn. Elsevier, Amsterdam
Knüpfer H, Preiss R (2007) Significance of interleukin-6 (IL-6) in breast cancer (review). Breast Cancer Res Treat 102:129–135
Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L (1998) Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 334(Pt 2):297–314
Kovacs E (2001) Investigation of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) in sera of cancer patients. Biomed Pharmacother 55(7):391–396
Kozłowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz MZ (2003) Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz Akad Med Bialymst 48:82–84
Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissière F, Laune D, Roques S, Lazennec G (2007) Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res 9(1):R15
Lyon DE, McCain NL, Walter J (2008) Cytokine comparison between women with breast cancer and women with a negative breast biopsy. Nurs Res 57(1):51–58
Akbulut H, Tang Y, Akbulut KG, Maynard J, Deisseroth A (2008) Chemotherapy targeted to cancer tissue potentiates antigen-specific immune response induced by vaccine for in vivo antigen loading and activation of dendritic cells. Mol Ther 16(10):1753–1760
Pusztai L, Mendoza TR, Reuben JM, Martinez MM, Willey JS, Lara J, Syed A, Fritsche HA, Bruera E, Booser D et al (2004) Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine 25(3):94–102
Lee M, Yea SS, Jeon YJ (2000) Paclitaxel causes mouse splenic lymphocytes to a state hyporesponsive to lipopolysaccharide stimulation. Int J Immunopharmacol 22(8):615–621
Nolen BM, Marks JR, Ta’san S, Rand A, Luong TM, Wang Y, Blackwell K, Lokshin AE (2008) Serum biomarker profiles and response to neoadjuvant chemotherapy for locally advanced breast cancer. Breast Cancer Res 10(3):R45
Llanes-Fernandez L, Alvarez-Goyanes RI, Arango-Prado Mdel C, Alcocer-Gonzalez JM, Mojarrieta JC, Perez XE, Lopez MO, Odio SF, Camacho-Rodríguez R, Guerra-Yi ME et al (2006) Relationship between IL-10 and tumor markers in breast cancer patients. Breast 15(4):482–489
Merendino RA, Arena A, Capozza AB, Chillemi S, Mesiti M (1996) Serum levels of interleukin-10 in patients affected by breast cancer. Immunol Lett 53(1):59–60
Merendino RA, Gangemi S, Misefari A, Arena A, Capozza AB, Chillemi S, D’Ambrosio FP (1999) Interleukin-12 and interleukin-10 production by mononuclear phagocytic cells from breast cancer patients. Immunol Lett 68(2–3):355–358
Son KS, Kang HS, Kim SJ, Jung SY, Min SY, Lee SY, Kim SW, Kwon Y, Lee KS, Shin KH et al (2010) Hypomethylation of the interleukin-10 gene in breast cancer tissues. Breast 19(6):484–488
Razmkhah M, Jaberipour M, Erfani N, Habibagahi M, Talei AR, Ghaderi A (2011) Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response? Cell Immunol 266(2):116–122
Heckel MC, Wolfson A, Slachta CA, Schwarting R, Salgame P, Katsetos CD, Platsoucas CD (2011) Human breast tumor cells express IL-10 and IL-12p40 transcripts and proteins, but do not produce IL-12p70. Cell Immunol 266(2):143–153
Rosen HR, Ausch C, Reinerova M, Zaspin E, Renner K, Rosen AC, Schiessel R, Moroz C (1998) Activated lymphocytes from breast cancer patients express the characteristics of type 2 helper cells—a possible role for breast cancer-associated p43. Cancer Lett 127(1–2):129–134
Rao VS, Alabi A, Dyer CE, Greenman J, Drew PJ (2008) IL-10 and IL-12 expression in breast cancer patients and effect of therapy—ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 26(15S):14016
Santos SCL, Ribeiro EMSF, Cavalli IJ, Lima RS, da Graça Bicalho M (2005) IL-10 gene polymorphisms and sporadic breast cancer. Hum Immunol 66(8), Supplement 1:53
Yu KD, Chen AX, Yang C, Fan L, Huang AJ, Shao ZM (2010) The associations between two polymorphisms in the interleukin-10 gene promoter and breast cancer risk. Breast Cancer Res Treat; doi:10.1007/s10549-010-1133-3
Giordani L, Bruzzi P, Lasalandra C, Quaranta M, Schittulli F, Della Ragione F, Iolascon A (2003) Association of breast cancer and polymorphisms of interleukin-10 and tumor necrosis factor-alpha genes. Clin Chem 49(10):1664–1667
Smith KC, Bateman AC, Fussell HM, Howell WM (2004) Cytokine gene polymorphisms and breast cancer susceptibility and prognosis. Eur J Immunogenet 31(4):167–173
Langsenlehner U, Krippl P, Renner W, Yazdani-Biuki B, Eder T, Köppel H, Wascher TC, Paulweber B, Samonigg H (2005) Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk. Breast Cancer Res Treat 90(2):113–115
Kong F, Liu J, Liu Y, Song B, Wang H, Liu W (2010) Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population. J Exp Clin Cancer Res 29:72
Gerger A, Renner W, Langsenlehner T, Hofmann G, Knechtel G, Szkandera J, Samonigg H, Krippl P, Langsenlehner U (2010) Association of interleukin-10 gene variation with breast cancer prognosis. Breast Cancer Res Treat 119(3):701–705
Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24(1):1–8
Kingo K, Ratsep R, Koks S, Karelson M, Silm H, Vasar E (2005) Influence of genetic polymorphisms on interleukin-10 mRNA expression and psoriasis susceptibility. J Dermatol Sci 37(2):111–113
Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P (1999) Polymorphic haplotypes of the interleukin-10 50 flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 42(6):1101–1108
Yang CH, Chuang LY, Chen YJ, Tseng HF, Chang HW (2011) Computational analysis of simulated SNP interactions between 26 growth factor-related genes in a breast cancer association study. OMICS 15(6):399–407
Acknowledgments
The authors are thankful to Indian Council of Medical Research (ICMR), Govt. of India for financial support by (Grant Number 5/13/12/2007-NCDIII). Hamidullah would like to thank Department of Biotechnology (DBT), Govt. of India for Junior Research Fellowship. CDRI communication number of this manuscript is 8143.
Conflict of interest
None of the authors have any conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hamidullah, Changkija, B. & Konwar, R. Role of interleukin-10 in breast cancer. Breast Cancer Res Treat 133, 11–21 (2012). https://doi.org/10.1007/s10549-011-1855-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-011-1855-x