{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:26:50Z","timestamp":1758814010680},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,9,27]],"date-time":"2004-09-27T00:00:00Z","timestamp":1096243200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Undifferentiated Nasopharyngeal Carcinoma (NPC) patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV) which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL) and tumor- infiltrating (TIL) lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10) and three immunoglobulin isotypes (IgM, IgG, IgA).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM) for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA). Data were analysed using Student's t-test and probability values below 5% were considered significant.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002), IL-10 (p = 0,020), IgM (p= 0,0003) and IgG (p &lt; 0,0001) than their PBL. On the other hand, patients PBL produced significantly higher levels of IL-2 (p = 0,022), IL-10 (p = 0,016) and IgM (p = 0,004) than those of controls. No significant differences for IL-6 and IgA were observed.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2407-4-68","type":"journal-article","created":{"date-parts":[[2004,9,30]],"date-time":"2004-09-30T06:23:47Z","timestamp":1096525427000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC) patients"],"prefix":"10.1186","volume":"4","author":[{"given":"Lilia","family":"Fliss-Jaber","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhia","family":"Houissa-Kastally","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Bouzouita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naceur","family":"Khediri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ridha","family":"Khelifa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,9,27]]},"reference":[{"key":"158_CR1","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1002\/1097-0142(197909)44:3<1029::AID-CNCR2820440335>3.0.CO;2-5","volume":"44","author":"K Shanmugaratnam","year":"1979","unstructured":"Shanmugaratnam K, Chan SH, de-The G, Goh JE, Khor TH, Simons MJ: Histopathology of nasopharyngeal carcinoma : correlations with epidemiology, survival rates and other biological characteristics. Cancer. 1979, 44: 1029-1044.","journal-title":"Cancer"},{"key":"158_CR2","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1038\/2281056a0","volume":"228","author":"H Zur Hausen","year":"1970","unstructured":"Zur Hausen H, Schulte-Holthausen H, Klein G: EB-virus DNA in biopsies of Burkitt's tumors and anaplastic carcinomas of nasopharynx. Nature. 1970, 228: 1056-1058.","journal-title":"Nature"},{"key":"158_CR3","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1128\/jvi.66.5.2689-2697.1992","volume":"66","author":"L Brooks","year":"1992","unstructured":"Brooks L, Yao QY, Rickinson AB, Young LS: Epstein-Barr latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1 and LMP2 transcripts. J Virol. 1992, 66: 2689-2697.","journal-title":"J Virol"},{"key":"158_CR4","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1128\/jvi.66.5.3257-3262.1992","volume":"66","author":"P Busson","year":"1992","unstructured":"Busson P, Mc Coy R, Sadler R, Gilligan K, Tursz T, Raab-Traub N: Consistent transcription of the Epstein-Barr LMP2 gene in nasopharyngeal carcinoma. J Virol. 1992, 66: 3257-3262.","journal-title":"J Virol"},{"key":"158_CR5","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.4049\/jimmunol.158.7.3325","volume":"158","author":"SP Lee","year":"1997","unstructured":"Lee SP, Tierney RJ, Thomas WA, Brooks JM, Rickinson AB: Conserved CTL epitopes within EBV latent membrane protein 2. The Journal of Immunology. 1997, 158: 3325-3334.","journal-title":"The Journal of Immunology"},{"key":"158_CR6","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<451::AID-IMMU451>3.0.CO;2-U","volume":"28","author":"R Khanna","year":"1998","unstructured":"Khanna R, Burrows SR, Nicholls J, Poulsen LM: Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1) : evidence for HLA A2 supertype-restricted immune recognition of EBV-infected cells by LMP1-specific cytotoxic T lymphocytes. Eur J Immunol. 1998, 28: 451-458. 10.1002\/(SICI)1521-4141(199802)28:02<451::AID-IMMU451>3.3.CO;2-L.","journal-title":"Eur J Immunol"},{"key":"158_CR7","doi-asserted-by":"publisher","first-page":"573","DOI":"10.4049\/jimmunol.165.1.573","volume":"165","author":"SP Lee","year":"2000","unstructured":"Lee SP, Chan AT, Cheung ST, Thomas WA, Croom Carter D, Dawson CW, Tsai CH, Leung SF, Johnson PJ, Huang DP: CTL control of EBV in nasopharyngeal carcinoma (NPC) : EBV-specific CTL responses in the blood and tumors of NPC patients and the antigen-processing function of the tumor cells. J Immunol. 2000, 165: 573-582.","journal-title":"J Immunol"},{"key":"158_CR8","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1016\/S0140-6736(79)91309-6","volume":"21","author":"SH Chan","year":"1979","unstructured":"Chan SH, Chew TS, Kunaratnam N: Cell-mediated immunity to Epstein-Barr virus in nasopharyngeal carcinoma. The Lancet. 1979, 21: 884-885. 10.1016\/S0140-6736(79)91309-6.","journal-title":"The Lancet"},{"key":"158_CR9","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1002\/ijc.2910390602","volume":"39","author":"M Lakhdar","year":"1987","unstructured":"Lakhdar M, Ellouz R, Kammoun H, Ben H'tira S, Khediri N, Kastally R, Fridman WH: Presence of in vivo activated T-cells expressing HLA-DR molecules and IL-2 receptors in peripheral blood of patients with nasopharyngeal carcinoma. Int J Cancer. 1987, 39: 663-669.","journal-title":"Int J Cancer"},{"key":"158_CR10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/BF01517046","volume":"37","author":"M Lakhdar","year":"1993","unstructured":"Lakhdar M, Thameur H, Maalej H, Ben Ayed F, Ladgham A: Emergence of non major histocopatibility complex restricted lytic CD8+ cells in the blood of naspharyngeal carcinoma. Cancer Immunol Immunother. 1993, 37: 131-139.","journal-title":"Cancer Immunol Immunother"},{"key":"158_CR11","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1002\/ijc.2910080212","volume":"8","author":"G Henle","year":"1971","unstructured":"Henle G, Henle W, Klein G: Demonstration of two distinct components in the early antigen complex of Epstein-Barr virus-infected cells. Int J Cancer. 1971, 8: 272-282.","journal-title":"Int J Cancer"},{"key":"158_CR12","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1002\/ijc.2910200504","volume":"20","author":"W Henle","year":"1977","unstructured":"Henle W, Ho JHS, Henle G, Chan JC, Kwan HC: Nasopharyngeal carcinoma : significance of changes in Epstein-Barr virus-related antibodies patterns following therapy. Int J Cancer. 1977, 20: 663-672.","journal-title":"Int J Cancer"},{"key":"158_CR13","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1006\/viro.1993.1597","volume":"197","author":"C Cochet","year":"1993","unstructured":"Cochet C, Martel-Renoir D, Grunewald V, Bosq J, Cochet G, Schwaab G, Bernaudin JF, Joab I: Expression of the Epstein-Barr virus immediate early gene, BZLF1, in nasopharyngeal carcinoma tumor cells. Virol. 1993, 197: 358-365. 10.1006\/viro.1993.1597.","journal-title":"Virol"},{"key":"158_CR14","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1126\/science.2161559","volume":"248","author":"KW Moore","year":"1990","unstructured":"Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR: Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRF1. Science. 1990, 248: 1230-1234.","journal-title":"Science"},{"key":"158_CR15","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1126\/science.2173142","volume":"250","author":"DH Hsu","year":"1990","unstructured":"Hsu DH, de Waal Malefyt R, Fiorentino DF: Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science. 1990, 250: 830-832.","journal-title":"Science"},{"key":"158_CR16","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/BF02785841","volume":"16","author":"F Salazar-Onfray","year":"1999","unstructured":"Salazar-Onfray F: Interleukin-10 : a cytokine used by tumors to escape immunosurveillance. Med Oncol. 1999, 16: 86-94.","journal-title":"Med Oncol"},{"key":"158_CR17","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/path.867","volume":"194","author":"A Beck","year":"2001","unstructured":"Beck A, Pazolt D, Grabenbauer GG, Nicholls JM, Herbst H, Young LS, Niedobitek G: Expression of cytokine and chemokine genes in Epstein-Barr virus-associated nasopharyngeal carcinoma : comparison with Hodgkin's disease. J Pathol. 2001, 194: 145-151. 10.1002\/path.867.","journal-title":"J Pathol"},{"key":"158_CR18","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1002\/(SICI)1097-0215(19970729)72:3<398::AID-IJC4>3.0.CO;2-K","volume":"72","author":"M Yao","year":"1997","unstructured":"Yao M, Ohshima K, Suzumiya J, Kume T, Shiroshita T, Kikuchi M: Interleukin-10 expression and cytotoxic-T-cell response in Epstein-Barr-virus-associated nasopharyngeal carcinoma. Int J Cancer. 1997, 72: 398-402. 10.1002\/(SICI)1097-0215(19970729)72:3<398::AID-IJC4>3.0.CO;2-K.","journal-title":"Int J Cancer"},{"key":"158_CR19","first-page":"1599","volume":"59","author":"YT Huang","year":"1999","unstructured":"Huang YT, Sheen TS, Chen CL, Lu J, Chang Y, Chen JY, Tsai CH: Profile of cytokine expression in nasopharyngeal carcinoma. Cancer Res. 1999, 59: 1599-1613.","journal-title":"Cancer Res"},{"key":"158_CR20","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1002\/(SICI)1097-0142(19990401)85:7<1439::AID-CNCR3>3.0.CO;2-6","volume":"85","author":"S Fujieda","year":"1999","unstructured":"Fujieda S, Lee K, Sunaga H, et al: Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma. Cancer. 1999, 85: 1439-1445. 10.1002\/(SICI)1097-0142(19990401)85:7<1439::AID-CNCR3>3.3.CO;2-Y.","journal-title":"Cancer"},{"key":"158_CR21","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/BF01200735","volume":"120","author":"M Tsukuda","year":"1993","unstructured":"Tsukuda M, Sawaki S, Yanoma S: Suppressed cellular immunity in patients with nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 1993, 120: 115-118.","journal-title":"J Cancer Res Clin Oncol"},{"key":"158_CR22","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1146\/annurev.iy.11.040193.001121","volume":"11","author":"KW Moore","year":"1993","unstructured":"Moore KW, O'Garra A, de Waal Malefyt R, Vieira P, Mosmann TR: Interleukin-10. Annu Rev Immunol. 1993, 11: 165-190. 10.1146\/annurev.iy.11.040193.001121.","journal-title":"Annu Rev Immunol"},{"key":"158_CR23","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1073\/pnas.89.5.1890","volume":"89","author":"F Rousset","year":"1992","unstructured":"Rousset F, Garcia E, Defrance T, Peronne C, Vezzio M, Hsu DH, Kastelin R, Moore KW, Banchereau J: Interleukin-10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA. 1992, 89: 1890-1893.","journal-title":"Proc Natl Acad Sci USA"},{"key":"158_CR24","doi-asserted-by":"publisher","first-page":"2815","DOI":"10.4049\/jimmunol.164.5.2815","volume":"164","author":"J Xu","year":"2000","unstructured":"Xu J, Ahmed A, D'addario M, Knafo L, Jones JF, Prazard U, Dolcetti R, Vaccher E, Menezes J: Analysis and significance of anti-latent membrane protein-1 antibodies in the sera of patients with EBV-associated disease. J Immunol. 2000, 164: 2815-2822.","journal-title":"J Immunol"},{"key":"158_CR25","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1126\/science.181845","volume":"193","author":"DA Morgan","year":"1976","unstructured":"Morgan DA, Ruscetti FW, Gallo R: Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976, 193: 1007-1008.","journal-title":"Science"},{"key":"158_CR26","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1084\/jem.167.2.332","volume":"167","author":"A Muraguchi","year":"1988","unstructured":"Muraguchi A, Hirano T, Tang B: The essential role of B cell stimulating factor (BSF-2\/IL-6) for the terminal differentiation of B-cells. J Exp Med. 1988, 167: 332-344. 10.1084\/jem.167.2.332.","journal-title":"J Exp Med"},{"key":"158_CR27","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1126\/science.169.3941.188","volume":"169","author":"W Henle","year":"1970","unstructured":"Henle W, Henle G, Azjac BA, Pearson G, Waubke R, Scriba M: Differential reactivity of human serums with early antigens induced by Epstein-Barr virus. Science. 1970, 169: 188-190.","journal-title":"Science"},{"issue":"suppl","key":"158_CR28","first-page":"81","volume":"97","author":"M Boyum","year":"1968","unstructured":"Boyum M: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest. 1968, 97 (suppl): 81-85.","journal-title":"Scand J Clin Lab Invest"},{"key":"158_CR29","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1093\/intimm\/4.7.747","volume":"7","author":"Y Ichiki","year":"1992","unstructured":"Ichiki Y, Takahashi W, Watanabe T: The effect of cytokines and mitogens on the induction of C epsilon germline transcripts in a human Burkitt lymphoma B cell line. Int Immunol. 1992, 7: 747-757.","journal-title":"Int Immunol"},{"key":"158_CR30","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0165-2427(00)00193-8","volume":"75","author":"BJ Hartnett","year":"2000","unstructured":"Hartnett BJ, Somberg RL, Krakowka S, Ochs HD, HogenEsch H, Moore PF, Wernberg KI, Felsburg PJ: B-cell function in canine X-linked severe combined immunodeficiency. Vet Immunol Immunopathol. 2000, 75: 121-134. 10.1016\/S0165-2427(00)00193-8.","journal-title":"Vet Immunol Immunopathol"},{"key":"158_CR31","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1128\/CDLI.5.1.78-81.1998","volume":"5","author":"RK Katial","year":"1998","unstructured":"Katial RK, Sachanandani D, Pinney C, Lieberman MM: Cytokine production in cell culture by peripheral blood mononuclear cells from immunocompetent hosts. Clin Diagn Lab Immunol. 1998, 5: 78-81.","journal-title":"Clin Diagn Lab Immunol"},{"key":"158_CR32","doi-asserted-by":"crossref","first-page":"981","DOI":"10.4049\/jimmunol.130.2.981","volume":"130","author":"R Suzuki","year":"1983","unstructured":"Suzuki R, Handa K, Itoh K, Kumagai K: Natural killer (NK) cells as a responder to interleukin 2 (IL-2). J Immunol. 1983, 130: 981-992.","journal-title":"J Immunol"},{"key":"158_CR33","doi-asserted-by":"crossref","first-page":"808","DOI":"10.4049\/jimmunol.148.3.808","volume":"148","author":"P Ralph","year":"1992","unstructured":"Ralph P, Nakoinz I, Sampson-Johannes A, Fong S, Lowe D, Min HY, Lin L: IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol. 1992, 148: 808-814.","journal-title":"J Immunol"},{"key":"158_CR34","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","volume":"136","author":"TR Mosmann","year":"1986","unstructured":"Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokines activities and secreted proteins. J Immunol. 1986, 136: 2348-2357.","journal-title":"J Immunol"},{"key":"158_CR35","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/S0952-7915(00)00162-X","volume":"12","author":"M Roncarolo","year":"2000","unstructured":"Roncarolo M, Levings MK: The role of different subsets of T regulatory cells in controlling autoimmunity. Curr Opin Immunol. 2000, 12: 676-683. 10.1016\/S0952-7915(00)00162-X.","journal-title":"Curr Opin Immunol"},{"key":"158_CR36","doi-asserted-by":"publisher","first-page":"6183","DOI":"10.4049\/jimmunol.170.12.6183","volume":"170","author":"NA Marshall","year":"2003","unstructured":"Marshall NA, Vickers MA, Barker RN: Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1. J Immunol. 2003, 170: 6183-6189.","journal-title":"J Immunol"},{"key":"158_CR37","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1182\/blood-2003-07-2594","volume":"103","author":"NA Marshall","year":"2004","unstructured":"Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN, Vickers MA: Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004, 103: 1755-1762. 10.1182\/blood-2003-07-2594.","journal-title":"Blood"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-4-68.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2407-4-68\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-4-68","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-4-68.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T12:36:09Z","timestamp":1728304569000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/1471-2407-4-68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,9,27]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2004,12]]}},"alternative-id":["158"],"URL":"https:\/\/doi.org\/10.1186\/1471-2407-4-68","relation":{},"ISSN":["1471-2407"],"issn-type":[{"type":"electronic","value":"1471-2407"}],"subject":[],"published":{"date-parts":[[2004,9,27]]},"assertion":[{"value":"17 May 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2004","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2004","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"68"}}