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Immunosuppression by micromolecular fibrinogen degradation products in cancer

Nature volume 259, pages 399–401 (1976)Cite this article

Abstract

PATIENTS with advanced cancer and lymphoid malignancies often show impaired cellular and humoral immune responses, partly caused by serum factors inhibiting lymphocyte reactivity1–3, which, although not fully defined, are considered to be low molecular weight (poly)peptides. Another frequent finding in malignant diseases is the appearance of circulating fibrin(ogen) degradation products (FDPs)4,5. Besides the commonly investigated breakdown products X, Y, D and E, plasmin liberates several small peptides from human fibrinogen designated “micromolecular FDPs”6. These are dialysable, thermostable, have molecular weights between 15,000 and 500 (ref. 6) and have distinct physiological properties7–10. Since both the degree of impairment of lymphocyte function and the frequency of FDP formation are related to the extent of neoplastic spread3,4, we investigated the influence of micromolecular FDPs on cellular and humoral immune responses. A striking immunosuppressive activity was found, possibly responsible for impaired immunoresponsiveness in cancer patients. Terminal FDPs were obtained by prolonged digestion of human fibrinogen (Forschungsfibrinogen Kabi) with human plasmin (Forschungsplasmin Kabi) in aqueous solution, pH 7.4, and dialysed against distilled water at 4 °C for 24 h. The dialysate was concentrated by evaporation in a vacuum, reconstituted in physiological saline, sterilised by filtration and added to lymphocyte cultures using a microculture system11. As Fig. 1 shows, micro-molecular FDPs caused a dose-dependent suppression of PHA-induced lymphocyte transformation, which was 98% at 1.1 mg m1−1. These concentrations did not affect cell viability as measured by Trypan blue exclusion. Plasmin dialysates alone, prepared in identical conditions, inhibited neither of the systems tested: separation of fibrinogen on Sephadex G-200 showed no evidence of pre-existing contaminants (Fig.4).

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References

  1. Scheurlen, P. G., Schneider, W., and Pappas, A., Lancet, ii, 1265 (1971).

    Article  Google Scholar 

  2. Glasgow, A. H., et al., New Engl. J. Med., 291, 1263–1267 (1974).

    Article  CAS  Google Scholar 

  3. Pappas, A., and Scheurlen, P. G., Verh. Dtsch. Ges. Inn. Med., 74, 1254–1256 (1968).

    CAS  PubMed  Google Scholar 

  4. Carlsson, S., Acta Chir. scand., 139, 499–502 (1973).

    CAS  PubMed  Google Scholar 

  5. Hedner, U., and Nilsson, M., Acta Med. scand., 189, 471–477 (1971).

    Article  CAS  Google Scholar 

  6. Triantaphyllopoulos, E., Prep. Biochem., 3 (5), 451–472 (1973).

    CAS  PubMed  Google Scholar 

  7. Stachurska, J., Latallo, Z., and Kopec, M., Thrombos. Diathes. Haemorrh., 23, 91–98 (1970).

    Article  CAS  Google Scholar 

  8. Buluk, K., and Malofiejew, M., Br. J. Pharmac., 35, 79–89 (1969).

    Article  CAS  Google Scholar 

  9. Niewiarowski, S., Ream, V. J., and Thomas, D. P., Thrombos. Diathes. Haemorrh. Suppl., 42, 49–59 (1971).

    Google Scholar 

  10. Larrieu, M. J., Scand. J. Haemat. Suppl., 13, 273–279 (1971).

    CAS  Google Scholar 

  11. Pees, H., and Pappas, A., Z. Immun.-Forsch., 150, 309–317 (1975).

    CAS  Google Scholar 

  12. Jerne, N. K., and Nordin, N. A. A., Science, 140, 405 (1963).

    Article  ADS  Google Scholar 

  13. Ogston, D., and Dawson, A. A., Acta Haemat., 49, 89–95 (1973).

    Article  CAS  Google Scholar 

  14. Scheurlen, P. G., Baake, M., Frey, N., Moers, P., and Sieberth, G., Dtsch. med. Wschr., 94, 17–23 (1969).

    Article  CAS  Google Scholar 

  15. Ambrus, J. L., Baliah, T., Ambrus, C. M., Mink, I. B., and Murphy, G. P., N. Y. State J. Med., 74, 1396–1402 (1974).

    CAS  PubMed  Google Scholar 

  16. Yu, V. Y. H., Waller, C. A., Maclennan, I. C. M., and Baum, J. D., Br. Med. J., 1, 428–432 (1975).

    Article  CAS  Google Scholar 

  17. Riggio, R. R., Schwartz, G. H., Bull, F. G., Stenzel, K. H., and Rubin, A. L., Transplantation, 8, 689–694 (1969).

    Article  CAS  Google Scholar 

  18. Dobbelstein, H., Klin. Wschr., 53, 461–466 (1975).

    Article  CAS  Google Scholar 

  19. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., J. biol. Chem., 193, 265–275 (1957).

    Google Scholar 

  20. Schwarze, G., and Scheurlen, P. G., Int. Archs Allerg., 46, 629–643 (1973).

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Medizinische Universitätsklinik und Poliklinik, D–665, Homberg, FRG

    G. GIRMANN, H. PEES, G. SCHWARZE & P. G. SCHEURLEN

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  1. G. GIRMANN
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  2. H. PEES
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  4. P. G. SCHEURLEN
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GIRMANN, G., PEES, H., SCHWARZE, G. et al. Immunosuppression by micromolecular fibrinogen degradation products in cancer. Nature 259, 399–401 (1976). https://doi.org/10.1038/259399a0

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