Skip to main content
SpringerLink
Log in

Human tumour-induced inhibition of interferon action in vitro: Reversal of inhibition by β-carotene (pro-vitamin A)

  • Original Articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Inhibitors of human interferon action that might be relevant to tumour resistance or escape mechanisms were investigated in a macrophage system. The effects of IFN on macrophage Fcγ receptor expression were inhibited by three preparations: (1) a low-molecular-weight component of normal autologous serum; (2) a low-molecular-weight component of carcinoma supernatant; and (3) physiological concentrations of retinol and retinoic acid. Since human carcinoma tissue contains abnormally high levels of retinoic acid-binding protein, the possibility that a tumour-associated retinoid contributes to tumour-induced inhibition in vitro was investigated. Inhibition of IFN action in vitro by retinoic acid (vitamin A acid) was found to be reversed by β-carotene (pro-vitamin A). When tested in the tumour system β-carotene also reversed inhibition by the human-carcinoma-derived signal. These data are consistent with the view that at least one of the tumour-derived signals inhibitory towards IFN is a tumour-associated retinoid, although firm evidence for this must await further physicochemical characterization of the inhibitory signal(s). The present data clearly show, nevertheless, that human tumour-induced inhibition of IFN in vitro can be reversed by the pro-vitamin β-carotene.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abb J, Abb H, Deinhardt F (1982) Effect of retinoic acid on the spontaneous and interferon-induced activity of human natural killer cells. Int J Cancer 30:307

    Google Scholar 

  2. Allen G, Fantes KH (1980) A family of structural genes for human lymphoblastoid (leukocyte-type) interferon. Nature 287:408

    Google Scholar 

  3. Baron S, Kleyn KM, Russell JK, Blalock JE (1981) Retinoic acid; enhancement of a tumour and inhibition of interferon's anti-tumour action. J Natl Cancer Inst 67:95

    Google Scholar 

  4. Boetcher DA, Leonard EJ (1974) Abnormal monocyte chemotactic response in cancer patients. J Natl Cancer Inst 52:1091

    Google Scholar 

  5. Cianciolo G, Hunter J, Silva J, Haskill JS, Snyderman R (1981) Inhibitors of monocyte responses to chemotaxis are present in human cancerous effussions and react with monoclonal antibodies to the P15E structural protein of retroviruses. J Clin Invest 68:831

    Google Scholar 

  6. Clamon GH, Nugent KM, Rossi NP (1981) Cellular retinoic acid binding proteins in human lung carcinomas. J Natl Cancer Inst 67:61

    Google Scholar 

  7. Currie GA, Hedley DW (1977) Monocytes and macrophages in malignant melanoma I. Peripheral blood macrophage precursors. Br J Cancer 36:1

    Google Scholar 

  8. Dennert G, Crowley C, Kouba J, Lotan R (1979) Retinoic acid stimulation of the induction of mouse killer T cells in allogeneic and syngeneic systems. J Natl Cancer Inst 62:89

    Google Scholar 

  9. Dean RT, Vireligier J-L (1983) Interferon as a macrophage activating factor. I. Enhancement of cytotoxicity by fresh and matured human monocytes in the absence of other soluble signals. Clin Exp Immunol 51:501

    Google Scholar 

  10. Dent RG, Cole P (1981) In vitro monocyte maturation in sqamous carcinoma of the lung. Br J Cancer 43:486

    Google Scholar 

  11. Dizon QS, Southam CM (1963) Abnormal cellular responses to skin abrasions in cancer patients. Cancer 16:1288

    Google Scholar 

  12. Fauve RM, Hevin B, Jacob H, Gaillard JA, Jacob F (1974) Anti-inflammatory effects of murine malignant cells. Proc Natl Acad Sci USA 71:4052

    Google Scholar 

  13. Hakim AA (1980) Lipid-like agents from human neoplastic cells suppress cell-mediated immunity. Cancer Immunol Immunother 8:133

    Google Scholar 

  14. Huber PR, Geyer E, King W, Matter A, Torhorst J, Eppenberger U (1978) Retinoic acid-binding protein in human breast cancer and dysplasia. J Natl Cancer Inst 61:1375

    Google Scholar 

  15. Jerrells TR, Dean JH, McCoy JL, Richardson GL, Herberman RB (1978) Role of suppressor cells in depression of in vitro lymphoproliferative responses of lung and breast cancer patients. J Natl Cancer Inst 61:1001

    Google Scholar 

  16. Lacour F, Delage G, Lacour J (1977) Diminution du pourcentage de phagocytes mononuclees chez les malade atteintes de cancer du sein. C R Acad Sci [D] (Paris) 284:2447

    Google Scholar 

  17. Matsubara S, Sujuki M, Ishida N (1980) Impaired induction of type II interferon in tumour bearing mice. Cancer Res 40:873

    Google Scholar 

  18. Matsubara S, Suzuki M, Nakamura M, Edo K, Ishida N (1980) Isolation of an inhibitor of type II interferon induction from tumour ascitic fluids. Cancer Res 40:2534

    Google Scholar 

  19. Mytar B, Zembala M, Uracz W, Czupryna A (1982) Cytostatic activity on tumour cells of monocytes from patients with gastrointestinal cancer. Cancer Immunol Immunother 13:190

    Google Scholar 

  20. Nelson DS, Nelson M, Farram E, Inoue Y (1981) Cancer and subversion of host defences. Aust J Exp Biol Med Sci 59:229

    Google Scholar 

  21. North RJ, Spitalny GL, Kirstein DP (1978) Anti-tumour defence mechanisms and their subversion. In: Waters H (ed) Handbook of cancer immunology, vol 2. Garland STPM Press, New York, p 187

    Google Scholar 

  22. Nyholm RE, Currie GA (1978) Monocytes and macrophages in malignant melanoma. II. Lysis of antibody coated erythrocytes as an assay of monocyte function. Br J Cancer 37:337

    Google Scholar 

  23. Ong DE, Page DT, Chytil F (1975) Retinoic acid binding protein: occurrence in human tumours. Science 190:60

    Google Scholar 

  24. Peto R, Doll R, Buckley JD, Sporn MB (1981) Can dietary β-carotene materially reduce human cancer rates? Nature 290:201

    Google Scholar 

  25. Pike MC, Snyderman R (1976) Depression of macrophage function by a factor produced by neoplasms: a mechanism for abrogation of immune surveillance. J Immunol 117:1243

    Google Scholar 

  26. Rhodes J (1977) Altered expression of human monocyte Fc receptors in malignant disease. Nature 265:253

    Google Scholar 

  27. Rhodes J (1983) Human interferon action: reciprocal regulation by retinoic acid and β-carotene. J Natl Cancer Inst 70:833

    Google Scholar 

  28. Rhodes J, Oliver S (1980) Retinoids as regulators of macrophage function. Immunology 40:467

    Google Scholar 

  29. Rhodes J, Stokes P (1982) Interferon-induced changes in the monocyte membrane: inhibition by retinol and retinoic acid. Immunology 45:531

    Google Scholar 

  30. Rhodes J, Bishop M, Benfield J (1979) Tumour surveillance: How tumours may resist macrophage-mediated host defence. Science 203:179

    Google Scholar 

  31. Rhodes J, Plowman P, Bishop M, Lipscomb D (1981) Human macrophage function in cancer: systemic and local changes detected by an assay for Fc receptor expression. J Natl Cancer Inst 66:423

    Google Scholar 

  32. Rhodes J, Jones DH, Bleehen NM (1983) Increased expression of human monocyte HLA-DR antigens and Fcγ receptors in response to human interferon in vivo. Clin Exp Immunol 53:739

    Google Scholar 

  33. Ruco LP, Procopio A, Uccini S, Baroni CD (1980) Increased monocyte phagocytosis in cancer patients. Eur J Cancer 16:1315

    Google Scholar 

  34. Snyderman R, Pike MC, Altman LC (1975) Abnormalities of leukocyte chemotaxis in human disease. Ann NY Acad Sci 256:386

    Google Scholar 

  35. Sporn MB, Newton DL (1979) Chemoprevention of cancer with retinoids. Fed Proc 38:2528

    Google Scholar 

  36. Yoshie O, Mellman ID, Broeze RJ, Garcia-Blanco M, Lengyel P (1982) Interferon action: effects of mouse α and β interferons on rosette formation, phagocytosis, and surface-antigen expression of cells of the macrophage-type line RAW 309 Cr. 1. Cell Immunol 73:128

    Google Scholar 

  37. Young RM, Sundharadas G, Cantarow WD, Kumar PR (1982) Purification and functional characterization of a low-molecular-weight immune modulating factor produced by Lewis lung carcinoma. Int J Cancer 30:517

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK

    John Rhodes & Philip Stokes

  2. Department of Surgery, Addenbrooke's Hospital, Cambridge

    Paul Abrams

Authors
  1. John Rhodes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip Stokes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Abrams
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rhodes, J., Stokes, P. & Abrams, P. Human tumour-induced inhibition of interferon action in vitro: Reversal of inhibition by β-carotene (pro-vitamin A). Cancer Immunol Immunother 16, 189–192 (1984). https://doi.org/10.1007/BF00205428

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00205428

Keywords

Search

Navigation