IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity

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The presence of interleukin (IL)-6 in peritoneal carcinomatous fluid (PCF) and its effect on immune cells composition in PCF in patients with advanced ovarian carcinoma was studied. In 21 out of 30 ovarian carcinoma patients, PCF IL-6 levels were found to exceed those seen in PCFs of patients with gastrointestinal cancer. IL-6 activity was higher in serous/mucinous than in endometrioid and undifferentiated ovarian carcinoma PCF (P = 0.05). Ovarian carcinoma PCF IL-6 activities were correlated with serum C-reactive protein levels (r = 0.65, P = 0.0000, n = 25). Ovarian carcinoma PCF leucocyte profile differed from that in blood with respect to: (i) lower percentage of NK and CD8+ and (ii) higher percentage of B and CD45RO+, CD14+ and HLA-DR+ cells. The proportions of CD45RO+ in blood were correlated with IL-6 levels in PCF. Corresponding to PCF ovarian carcinoma tumours were stained for the presence of Ki-67 antigen and p53. The highest proportions of Ki-67+ cells and cells showing accumulation of p53 were seen in undifferentiated tumours. A low grade of p53 staining was seen in tumours associated with high IL-6 levels in PCF. It was evident that IL-6 production (i) depended on the histiotype of the tumour, (ii) influenced the local immune system in favour of accumulation of B, and T memory cells, and (iii) was higher in patients lacking p53 accumulation. © 2000 Cancer Research Campaign

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  1. Arinaga S, Karimine N, Nanbara S, Inoue H, Nakashima H, Ueo H and Akiyoshi T (1994) Lymphokine-activated killer cell activity of peripheral blood, spleen, regional lymph node, and tumour infiltrating lymphocytes in gastric cancer patients. J Surg Oncol 55: 179–185

  2. Asschert JG, Vellenga E, Hollema H, van der Zee AG and de-Vries EG (1997) Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6, (IL-6), interleukin-1 beta IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas. Eur J Cancer 33: 2246–2251

  3. Berek JS, Chung C, Kaldi K, Watson JM and Knox RM Martinez-Maza (1991) O Serum interleukin 6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol 164: 1038–1043

  4. Berger DP, Herbstritt L, Dengler WA, Marme D, Mertelsmann R and Fiebig HH (1995) Vascular endothelial growth factor (VEGF) mRNA expression in human tumor models of different histologies. Ann Oncol 6: 817–825

  5. Blay JY, Rossi JF, Wijdenes J, Menetrier-Caux C, Schemann S, Negrier S and Philip T Favrot-M (1997) Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma. Int J Cancer 72(3): 424–430

  6. Boury NM, Stabel TJ, Kehrli M Jr and Taylor M (1997) Comparison of the PK(15)- and WEHI 164 (clone 13)-based bioassays for detection of porcine tumor necrosis factor. Am J Vet Res 58: 1115–1119

  7. Cattoretti G, Becker M, Key G, Duchrow M, Schluter C, Galle J and Gerdes J (1992) Monoclonal antibodes against recombinant parts of the Ki-67 antigen (Mib 1 and Mib 3) detect proliferating cells in microwave-processed formalid-fixed paraffin sections. J Pathol 168: 357–363

  8. Cao X, Chen C, Zhang W, Tao Q, Yu Y and Ye T (1996) Enhanced efficacy of combination of IL-2 gene and IL-6 gene-transfected tumor cells in the treatment of established metastatic tumors. Gene Ther 3: 421–426

  9. Chang SG, Lee SJ, Lee SJ, Kimi JI, Jung JC, Kim H and Hoffman RM (1997) Interleukin-6 production in primary histoculture by normal human kidney and renal tumor tissues. Anticancer Res 17: 113–115

  10. Eskandari M, Nguyen D, Kunkel S and Remik D (1990) WEHI 164 subclone 13 assay for TNF: sensitivity, specificity, and reliability. Immunol Invest 19: 69–79

  11. Fennelley D (1995) Dose intensity in advanced ovarian cancer: have we answered the question?. Clin Cancer Res 1: 575–582

  12. Freedman RS, Tomasovic B, Templin S, Atkinson EN, Kudelka A, Edwards CL and Platsoucas CD (1994) Large-scale expansion in interleukin-2 of tumor-infiltrating lymphocytes from patients with ovarian carcinoma for adoptive immunonotherapy. J Immunol Method 167: 145–160

  13. Gastl G, Plante M, Finstad CL, Wong GY, Federici MG, Bander NH and Rubin SC (1993) High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer. Br J Haematol 83: 433–441

  14. Giannios J and Ioannidou-Mouzaka L (1997) Molecular aspects of breast and ovarian cancer. Eur J Gynaecol Oncol 18: 387–393

  15. Gotlieb WH, Watson JM, Rezai A, Johnson M, Martinez-Maza O and Berek JS (1994) Cytokine-induced modulation of tumor suppression gene expression in ovarian cancer cells: up-regulation of p53 gene expression and induction of apoptosis by tumor necrosis factor-α. Am J Obstet Gynecol 170: 1121–1130

  16. Hsu SM, Waldron JWJR, Hsu PL and Hough AJ Jr (1993) Cytokines in malignant lymphomas: review and prospective evaluation. Hum Pathol 24: 1040–1057

  17. Hutchins D and Steel C (1994) Regulation of ICAM-1(CD54) expression in human breast cancer cell lines by interleukin 6 and fibroblast-derived factors. Int J Cancer 58: 80–84

  18. Kishimoto T (1989) The biology of IL-6. Blood 74: 1–10

  19. Kutteh C (1992) Quantitation of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in the effusion of ovarian epithelial neoplasms. Am J Obstet Gynecol 167: 1864–1869

  20. Luca M, Huang S, Gershenwald JE, Singh RK, Reich R and Bar-Eli M (1997) Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 151: 1105–1113

  21. Machelon V, Nome F, Durand-Gasselin I and Emilie D (1997) Tumor necrosis factor-alpha induces interleukin-6 mRNA and protein in human granulosa luteinizing cells via protein tyrosine kinase without involving ceramide. Mol Cell Endocrinol 126: 173–184

  22. Matsuda M, Petersson M, Lenkei R, Taupin JL, Magnusson I, Mellstedt H, Anderson P and Kiessling R (1995) Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. Int J Cancer 61: 765–772

  23. Offner FA, Obrist P, Stadlmann S, Feichtinger H, Klingler P, Herold M, Zwierzina H, Hittmair A, Mikuz G and Abendstein B (1995) IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells. Cytokine 7: 542–547

  24. Oncolink – NCI/PDQ: Ovarian epithelial cancer – updated 04/97 (

  25. Papadopoulos NG, Dedoussis GV, Baxevanis CN and Papamichail M (1995) Bioassay vs. immunoassay for quantification of interleukin-6 in biological fluids. J Clin Lab Anal 9: 234–237

  26. Plante M, Rubin SC, Wong GY, Federici MG, Finstad GL and Gastl GA (1994) Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer 73: 1882–1887

  27. Runnebaum I (1997) Basics of cancer gene therapy. Anticancer Res 17: 2887–2890

  28. Schondorf T, Engel H and Lindemann C (1997) Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating lymphocytes in patients with gynaecological tumours. Cancer Immunol Immunother 44: 88–96

  29. Takatsuki F, Okano A, Suzuki C, Chieda R, Takahara Y, Hirano T, Kishimoto T, Hamuro J and Akiyama Y (1998) Human recombinant interleukin 6/B cell stimulatory factor 2 (IL-6/BSF-2) augments murine antigen-specific antibody responses. In vitro and in vivo. J Immunol 141: 3072

  30. Unutmaz D, Piler P and Abrignani S (1994) Antigen-independent activation of naive and memory resting T cells by a cytokine combination. J Exp Med 180: 1159–1164

  31. Willemse PH, de Vries EG, Mulder NH, Aalders JG, Bouma J and Sleijfer DT (1990) Intraperitoneal human recombinant interferon alpha 2b in minimal residual ovarian cancer. Eur J Clin Oncol 26: 353–358

  32. Wimmenauer S, Keller H, Rahner S, Kirste G, Von-Bergwelt M, Meyer A, Von-Kleist S and Farthmann EH (1994) Phenotypical and functional characteristics of tumor-infiltrating lymphocytes from colon carcinomas stimulated with rIL-2 and rIL-4 in vitro: comparison with lymphocytes of the normal colon mucosa and the peripheral blood. Anticancer Res 14: 963–968

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Kryczek, I., Gryboś, M., Karabon, L. et al. IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity. Br J Cancer 82, 621–628 (2000) doi:10.1054/bjoc.1999.0973

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  • ovarian carcinoma
  • IL-6
  • Ki-67
  • p53
  • carcinomatous effusion
  • phenotype

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