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Tumor-associated antigens are cytokine inducers and hyporeactivity factors to the immune system

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Biotherapy

Abstract

We investigated possible mechanisms leading to the inhibition of theimmune system in people with chronic disorders. Tumor cell produce proteinreleased into the circulation, such as tumor associated antigens, may playan important role in processes preceding paralysis of the immune system. Totest this hypothesis the following tumor associated antigens were used: AFP,OFP, CA-125, CA-50 and CA-19-9. Their role was assessed by modulatingcytokine production in cord blood lymphocytes and peripheral white bloodcells obtained from grown population of patients treated with colostrinin,an cytokine inducer. PHA, LPS and colostrinin were used as positive controlin those essays. Each antigen tested individually induced IFN, TNFαand IL-6 in dose dependent fashion. None of the tested cytokines werespontaneously released by the cells. Data generated from these experimentsindicated that tumor associated antigens are inducing type 1 cytokines insimilar fashion as LPS or colostrinin. However, lymphocytes taken frompatients undergoing therapy with colostrinin revealed progressive losscapability to produce type 1 cytokines as they did in case of colostrinin.The loss of the capability to respond to antigen may represent phenomenonleading to immune tolerance.

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References

  1. Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer JP. Colorectal carcinoma antigens detected by hybridoma antibodies. Somat. Cell. Mol. Gen. 1979; 5: 957–972.

    Google Scholar 

  2. Koprowski H, Herlyn M, Steplewski Z, Sears HF. Specific antigen in serum of patients with colon carcinoma. Science 1981; 212: 53–55.

    Google Scholar 

  3. Atkinson BF, Ernst CS, Herlyn M, Steplewski Z, Sears HF, Koprowski H. Gastrointestinal cancer-associated antigen in immunoperoxidase assay. Cancer Res 1982; 42: 4820–4823.

    Google Scholar 

  4. Magnani JL, Steplewski Z, Koprowski H, Ginsburg V. Identifi-cation of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res. 1983; 43: 5489–5492.

    Google Scholar 

  5. Olding LB, Thurin J, Svalander C, Koprowski H. Expression of gastrointestinal carcinoma-associated antigen (GICA) detected in human fetal tissues by monoclonal antibody. NS-19-9. Int. J. Cancer 1984; 34: 187–192.

    Google Scholar 

  6. Raux H, Labbe F, Fondaneche MC, Koprowski H, Burtin P. A study of gastrointestinal cancer-associated antigen (GICA) in human fetal organs. Int. Cancer 1983; 32: 315–319.

    Google Scholar 

  7. Tizzani A, Casetta G, Ciciogoi A, Piana P, Cerchier A, Pecchio F, Piantino P. Tumor markers (CEA, TPA and CA 19-9) in urine of bladder cancer patients. Int. J. Biol. Markers 1987; 2: 121–124.

    Google Scholar 

  8. Hakomori S. Possible functions of tumor-associated carbohydrate antigens. Curr. Opin. Immunol 1991; 3: 646–653.

    Google Scholar 

  9. Nakayama T, Watanabe M, Katsumata T, Teramoto T, Kitajima M. Expression of sialyl Lewis(a) as a new prognostic factor for patients with advanced colorectal carcinoma. Cancer 1995; 75: 2051–2056.

    Google Scholar 

  10. Klopocki AG, Krop-Watorek A, Dus D, Ugorski M. Adhesion of human uroepithelial cells to E-selectin: possible involvment of sialosyl Lewis a-ganglioside. Int. J. Cancer 1996; 68}: 239–

    Google Scholar 

  11. Janusz M, Staroscik K, Zimecki M, Wieczorek Z, Lisowski J. Chemical and physical characterization of a proline-rich polypeptide from sheep colostrum. Biochem. J. 1981; 199: 9–15.

    Google Scholar 

  12. Janusz M, Lisowski J. Proline-rich polypeptide (PRP)-an immunomodulatory peptide from ovine colostrum. Arch. Immunol. et Ther. Expl. 1993; 41: 275–279.

    Google Scholar 

  13. Inglot AD, Janusz M, Lisowski J. Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes. Arch. Immunol. et Ther. Expl. 1996; 44: 215–224.

    Google Scholar 

  14. Piasecki E, Inglot AD, Winiarska M, Krukowska K, Janusz M, Lisowski J. Coincidence between spontaneous release of interferon and tumor necrosis factor by colostral leukocytes and the production ofa colostrinin by human mammary gland after normal delivery. Arch. Immunol. et Ther. Expl. 1997; 45: 109–117.

    Google Scholar 

  15. Georgiades JA, Gelder F, Inglot A. Isolation and preliminary characterization of a new cytokine in human colostrum; its similarity to ovine colostrinine. Eur. Cytokine Netw. 1996: 7: 511.

    Google Scholar 

  16. Stringfellow DA. Regulation of interferon production and hyporesponsiveness. Interferon System. Texas Reports on Biology and Med. Baron S, Dianzani N, Stanton GJ eds. Univ. of Texas, Austin, USA. 1997, 83–88.

    Google Scholar 

  17. Ho M, Kono Y, Breining MK. Tolerance to the induction of interferons by endotoxin and virus: role of a humoral factor. Proc. Soc. Exp. Biol. Med. 1965; 119: 1227–1232.

    Google Scholar 

  18. Levy HB, Salazar AM. Interferon inducers. Interferon: Principles and Medical Applications eds. Baron S. et al. (The University of Texas Medical Branch at Galveston Dept. of Microbiol. Galveston TX USA) 1992; 65–76.

    Google Scholar 

  19. Yamamoto JK, Kruzel L, Louie H, Georgiades JA. Inhibition of human immunodeficiency virus type I replication by human interferons alpha, beta and gamma. Arch Immunol. et Ther. Expl 1993; 41: 185–192.

    Google Scholar 

  20. Leszek J, Inglot AD, Janusz M, Lisowski J. Therpeutic effi-cacy of colostrinine in Alzheimer's disease Suppl. to Biol. Psychiatry 1997, 42 (1S) Abstract 39–29.

    Google Scholar 

  21. Tishon A, Borrow P, Oldstone MBA. Virus-induced immuno-suppression. Age at infection relates to a selective or generalized defect. Virology 1993; 195: 397–405.

    Google Scholar 

  22. Cheynier R, Langlade-Demoyen P, Marescot MR, Blanche S, Blandin G, Wain-Hobson S, Griscelli C, Vilmer E, Plato F. Cytoxic T lymphocyte responses in the peripheral blood of children born to human immunodefciency virus-1-infected mothers. Europ. J. Immunol. 1992; 22: 2211–2217.

    Google Scholar 

  23. Field C, Wildy P. The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J. Hyg. 1978; 81: 267–277.

    Google Scholar 

  24. Penna A, Chisari FV, Bartoletti A, Missale G, Fowler O, Giuberti T, Ficcadori F, Ferrari C. Cytoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatiits B virus nucleocapsid antigen. J. Expl. Med. 1991; 174: 1565–1570.

    Google Scholar 

  25. Taylor PM, Davey J, Howland K, Ruthbard J, Ascona BA. Class I MHC molecules rather than other mouse genes dictate influeza epitope recognition by cytoxic T cells. Immunotherapies 1987; 26: 267–272.

    Google Scholar 

  26. Wu-Hsein B, Howard DH, Ahmed R. Virus-induced immunosupression a murine model of susceptibility to opportunistic infection. J. Infect Dis. 1988; 158: 232–235.

    Google Scholar 

  27. Teichman JV, Sieber G, Ludwig WD, Ruehl H. Immunosupressive effects of recombinant interferon-alpha during long-term treatment of cancer patients. Cancer 1989; 63: 1990–1993.

    Google Scholar 

  28. Gangopadhyay A, Bajenova O, Kelly TM, Thomas P. Carcinoembryonic antigen induces cytokine expression in Kuppfer cells: implications for hepatic metastasis from colorectal cancer. Cancer Res. 1996; 56: 4805–4810.

    Google Scholar 

  29. Bocci V. x of interferon? Clin. Pharmacokin. et. 1991; 21: (6) 411–417.

    Google Scholar 

  30. Goldman AB, Chheda S, Garafolo R, Schmalsteig FC. Cytokine in human milk: properties and potential effects upon the mammary gland and the neonate. J. Mamm. Gland Biol. and Neoplasia 1996; 1: 251–258.

    Google Scholar 

  31. Bocci V, Von Bremen K, Corradeschi E, Luzzi E, Paulescu L. What is the orle of cytokines in human colostrum? J. Biol. Regulators and Homeost Agents 1991; 5: (4) 121–124.

    Google Scholar 

  32. Garofolo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalsteig FC, Rassin DK Goldman AS. Interleukin-10 in human milk. Pediatric Res. 1995; 37: (4) 444–448.

    Google Scholar 

  33. Cembrzynska-Nowak M, Szklarz E, Inglot AD. Modulation of cytokine production by a selenoorganic compound (AE22) in hyperreactive or hyporeactive bronchio alveolar leukocytes of asthmatics or lung cancer patients J. Interferon Cyt. Res. 1997; 17: 609–617.

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Virology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114, Wroclaw, Poland

    Anna D Inglot

  2. School of Medicine, Louisiana State University Medical School, Shreveport, LA, 71130

    Frank Gelder

  3. The Georgiades-Foundation for the Treatment of Chronic Viral Diseases, Stafford, TX, 77477

    Jerzy A. Georgiades

Authors
  1. Anna D Inglot
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  2. Frank Gelder
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  3. Jerzy A. Georgiades
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Inglot, A.D., Gelder, F. & Georgiades, J.A. Tumor-associated antigens are cytokine inducers and hyporeactivity factors to the immune system. Biotherapy 11, 27–37 (1998). https://doi.org/10.1023/A:1007936706416

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  • DOI: https://doi.org/10.1023/A:1007936706416