Cancer Immunology, Immunotherapy

, Volume 7, Issue 4, pp 263–269 | Cite as

A mechanism of suppression of antitumor immunity (LAI reactivity) by surgery

  • N. Grosser
  • D. M. P. Thomson
  • M. Flores
  • J. K. MacFarlane
Original Articles
Received:
Accepted:

Summary

Antitumor immunity assayed by tube leukocyte adherence inhibition (LAI) is suppressed during and for up to 1–3 weeks after surgery. The results of this study suggest that when cortisol is elevated above physiologic levels by the stress of surgery this has a marked suppressive effect on the LAI-reactive cell. Cortisol added to the in vitro tube LAI assay had a two-phase effect. Cortisol at concentrations about two-fold above physiologic levels inhibited the sensitization of the peripheral blood leukocytes with cytophilic IgG antitumor antibody; however, if the cell was already armed, the cortisol did not negate its LAI reactivity. Higher concentrations of cortisol had a direct inhibitory effect on the LAI-reactive cells' ability to react with tumor antigen whether or not the cells were armed. In addition, the in vivo elevation of cortisol by the administration of cortisone acetate to LAI-positive patients inhibited the LAI reactivity of their leukocytes. Stress-induced elevation of cortisol by surgery may have an adverse effect on resistance to tumor growth, and the extent of the immunodepression may be one of the variables in the difference in survival of patients with cancers with similar degrees of invasion.

Keywords

Acetate Adverse Effect Cortisol Tumor Growth Cancer Research 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Agosin, M., Christen, R., Badinez, O., Gasic, G., Neghme, A., Pizarro, O., Jarpa, A.: Cortisone-induced metastases of adenocarcinoma in mice. Proc. Soc. Exp. Biol. Med. 80, 128 (1952)Google Scholar
  2. 2.
    Agostino, D., Cliffton, E.: Anesthetic effect on pulmonary metastases in rats. Arch. Surg. 88, 735 (1964)Google Scholar
  3. 3.
    Baserga, R., Shubik, P.: The action of cortisone on transplanted and induced tumors in mice. Cancer Res. 14, 12 (1954)Google Scholar
  4. 4.
    Berenbaum, M. C., Fluck, P. A., Hurst, N. P.: Depression of lymphocyte responses after surgical trauma. Br. J. Exp. Pathol. 54, 597 (1973)Google Scholar
  5. 5.
    Boeryd, B., Rudenstam, C.: Effect of heparin plasminogen inhibitor (eaca) for trauma of tumor metastases. Acta Pathol. Microbiol. Scand. 69, 28 (1967)Google Scholar
  6. 6.
    Butler, W., Rossen, R.: Effects of corticosteroids on immunity in man. I. Decreased serum IgG concentration caused by 3 or 5 days of high doses of methylprednisolone. J. Clin. Invest. 52, 2629 (1973)Google Scholar
  7. 7.
    Claman, H. N.: How corticosteroids work. J. Allergy Clin. Immunol. 55, 145 (1975)Google Scholar
  8. 8.
    Cochran, A. J., Spilg, W. G. S., Mackie, R. M., Thomas, C. E.: Postoperative depression of tumour-directed cell-mediated immunity in patients with malignant disease. Br. Med. J. 1972 IV, 67Google Scholar
  9. 9.
    Crile, G.: The danger of surgical dissemination of papillary carcinoma of the thyroid. Surg. Gynecol. Obstet. 102, 161 (1956)Google Scholar
  10. 10.
    Dimitriu, A.: Suppression of macrophage arming by corticosteroids. Cell. Immunol. 21, 79 (1976)Google Scholar
  11. 11.
    Eccles, S. A., Alexander, P.: Immunologically-mediated restraint of latent tumour metastases. Nature 257, 52 (1975)Google Scholar
  12. 12.
    Fauci, A. S., Dale, D. C., Balow, J. E.: Glucocorticosteroid therapy: Mechanisms of action and clinical considerations. Ann. Intern. Med. 84, 304 (1976)Google Scholar
  13. 13.
    Fischer, B., Fischer, E.: Experimental studies in factors influencing hepatic metastases. Ann. Surg. 50, 731 (1959)Google Scholar
  14. 14.
    Flores, M., Marti, J. H., Grosser, N., MacFarlane, J. K., Thomson, D. M. P.: An overview: antitumor immunity in breast cancer assayed by tube leukocyte adherence inhibition. Cancer 39, 494 (1977)Google Scholar
  15. 15.
    Fried, I. A.: The influence of the anaesthetic on survival rates of breast cancer patients after surgery. Int. J. Cancer 20, 213 (1977)Google Scholar
  16. 16.
    Fried, I. A., Yaremenko, K. V.: The influence of anaesthesia on metastasis development following surgical operation. Vopr. Onkol. 20, 43 (1974) [In Russian]Google Scholar
  17. 17.
    Greco, R. S., Dick, L., Duckenfield, J.: Perioperative suppression of the leukocyte migration inhibition assay in patients undergoing elective operations. Surg. Gynecol. Obstet. 147, 717 (1978)Google Scholar
  18. 18.
    Grosser, N., Thomson, D. M. P.: Cell-mediated antitumour immunity in breast cancer patients evaluated by antigen-induced leukocyte adherence in test tubes. Cancer Res. 35, 2571 (1975)Google Scholar
  19. 19.
    Grosser, N., Marti, J. H., Proctor, J. W., Thomson, D. M. P.: Tube leukocyte adherence inhibition assay for the detection of anti-tumour immunity. I. Monocyte is the reactive cell. Int. J. Cancer 18, 39 (1976)Google Scholar
  20. 20.
    Hibbs, J. B., Jr.: Heterocytolysis by macrophages activated by bacillus Calmette-Guérin: lysosome exocytosis into tumor cells. Science 184, 468 (1974)Google Scholar
  21. 21.
    Howard, R. J., Simmons, R. L.: Acquired immunologic deficiencies after trauma and surgical procedures. Surg. Gynecol. Obstet. 139, 771 (1974)Google Scholar
  22. 22.
    Lindberg, R. E., Frenkel, J. K.: Cellular immunity to toxoplasma and besnoitia in hamsters: specificity and the effects of cortisol. Infect. Immun. 15, 855 (1977)Google Scholar
  23. 23.
    Lundy, J., Lovett, E. J., Wolinsky, S. M., Conran, P.: Immune impairment and metastatic tumor growth. The need for an immunorestorative drug as an adjunct to surgery. Cancer 43, 945 (1979)Google Scholar
  24. 24.
    Marti, J., Thomson, D. M. P.: Anti-tumour immunity in malignant melanoma assay by tube leucocyte-adherence inhibition. Br. J. Cancer 34, 116 (1976)Google Scholar
  25. 25.
    Marti, J. H., Grosser, N., Thomson, D. M. P.: Tube leukocyte adherence inhibition assay for the detection of anti-tumour immunity: II. Monocyte reacts with tumour antigen via cytophilic anti-tumour antibody. Int. J. Cancer 18, 48 (1976)Google Scholar
  26. 26.
    Munster, A. M., Eurenius, K., Katz, R. M., Canales, L., Foley, F. D., Mortensen, R. F.: Cell-mediated immunity after thermal injury. Ann. Surg. 177, 139 (1973)Google Scholar
  27. 27.
    Park, S. K., Brody, J. I., Wallace, H. A., Blakemore, W. S.: Immunosuppressive effect of surgery. Lancet 1971 I, 53Google Scholar
  28. 28.
    Pomeroy, T. C.: Studies on the mechanism of cortisone-induced metastases of transplantable mouse tumors. Cancer Res. 14, 201 (1954)Google Scholar
  29. 29.
    Riddle, P. R., Berenbaum, M. C.: Postoperative depression of the lymphocyte response to phytohemagglutinin. Lancet 1967 I, 746Google Scholar
  30. 30.
    Roberts, S. S., Hengesh, J. W., McGrath, R. G., Valaitis, J., McGrew, E. A., Cole, W. H.: Prognostic significance of cancer cells in the circulating blood. A ten year evaluation. Am. J. Surg. 113, 757 (1967)Google Scholar
  31. 31.
    Sandberg, A. A., Eik-Nes, K., Samuels, L. T., Tyler, F. H.: The effects of surgery on the blood levels and metabolism of 17-hydroxycorticosteroids in man. J. Clin. Invest. 33, 1509 (1954)Google Scholar
  32. 32.
    Selye, H.: The general adaptation syndrome and the diseases of adaptation. J. Clin. Endocrinol. 6, 117 (1946)Google Scholar
  33. 33.
    Slade, M. S., Simmons, R. L., Yunis, E., Greenberg, L. J.: Immunodepression after major surgery in normal patients. Surgery 78, 363 (1975)Google Scholar
  34. 34.
    Tataryn, D. N., MacFarlane, J. K., Murray, D., Thomson, D. M. P.: Tube leukocyte adherence inhibition (LAI) assay in gastroiintestinal (GIT) cancer. Cancer 42, 112 (1979)Google Scholar
  35. 35.
    Timoshechkina, M. E.: The effect of surgical trauma on sarcoma-45 development during anaesthesia. Vopr. Onkol. 13, 92–95 (1967) [In Russian]Google Scholar
  36. 36.
    Vose, B. M., Kimber, I.: The effects of halothane anaesthesia on antibody-dependent cellular cytotoxicity in rats. Immunology 32, 609 (1977)Google Scholar
  37. 37.
    Vose, B. M., Moudgil, G. C.: Effect of surgery on tumour-directed leucocyte responses. Br. Med. J. 1975 I, 56Google Scholar
  38. 38.
    Vose, B. M., Moudgil, G. C.: Post-operative depression of antibody-dependent lymphocyte cytotoxicity following minor surgery and anaesthesia. Immunology 30, 123 (1976)Google Scholar
  39. 39.
    Yaremenko, K. V., Fried, I. A.: The functional activity of the pituitary-adrenal system and development of metastases of experimental tumours. Vopr. Onkol. 19, 77 (1973) [In Russian]Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • N. Grosser
    • 1
  • D. M. P. Thomson
    • 1
  • M. Flores
    • 1
  • J. K. MacFarlane
    • 1
  1. 1.Montreal General Hospital Research Institute, Montreal General Hospital, Division of Clinical Immunology and Department of SurgeryMontrealCanada

Personalised recommendations