Klinische Wochenschrift

, Volume 60, Issue 3, pp 121–131 | Cite as

Patients' immune response to breast and lung carcinoma-associated thomsen-friedenreich (T) specificity

  • G. F. Springer
  • S. M. Murthy
  • P. R. Desai
  • W. A. Fry
  • H. Tegtmeyer
  • E. F. Scanlon
Originalien

Summary

We report here sensitive and specific measurement of immune responses of patients with certain kinds of carcinoma toward the physically and chemically well defined T antigen isolated from healthy human erythrocytes. Over 90% of adenocarcinoma tissues tested possess T-specific immunoreactive structures as determined withhuman antisera, in contrast to healthy tissues and benign lesions. Adenocarcinoma patients recognize the carcinoma-associated T antigen as foreign. Delayed-type skin hypersensitivity reaction to T antigen (DTHR-T) was positive in all 25 lung adenocarcinoma patients tested, in 88% of 101 patients with ductal, in 43% of 30 patients with lobular or tubular breast carcinoma and in 9/9 patients with adenocarcinoma of body cavities. Patients of all Stages reacted positively. All 7 patients with small cell lung carcinoma and 3/5 with malignant melanoma had a positive DTHR-T. None of 17 patients with malignant brain tumors, leukemia or Hodgkin's disease, sarcoma or thyroid carcinoma reacted. The DTHR-T was specific in that all 77 healthy persons and 48/49 with other diseases, including 23/24 with non-cancer lung disease were negative; one patient with organizing interstitial pneumonitis was positive. This points to a possible source of false positive reactions. 91% of 149 patients with histologically benign breast disease had a negative DTHR-T; the histology of some of the positive ones was reexamined, 2 proved to have carcinoma in situ.

In vitro leukocyte migration inhibition and scoring of anti-T hemagglutinin titer using the T-anti-T system diagnosed many adenocarcinomata correctly, including 4 whose histology, while turning positive later, was negative at the time. However, these tests were generally less sensitive and specific than the DTHR-T.

This system may also be of screening and monitoring value. Surgical removal of primary carcinoma led to a rebound of anti-T in breast carcinoma patients and its renewed decrease in some, prior to clinical recurrence of cancer. Also, the DTHR-T turned from positive to negative in some Stages I and II breast-and T1–2 N0–1 M0 lung adenocarcinoma patients who had no demonstrable relapse during the ensuing observation period.

Key words

T Antigen and carcinoma Anti-T antibody and carcinoma Delayed-type hypersensitivity to carcinoma-associated T antigen Adenocarcinoma-associated T specificity 

Immunantwort von Patienten gegen Brust- und Lungen-karzinom-assoziiertes T-spezifisches Antigen

Zusammenfassung

Wir berichten hier über sensitive und spezifische Bestimmung der Immunatwort von Patienten mit Brust- und Lungenadenokarzinom gegen das physikalisch und chemische definierte T Antigen, isoliert von menschlichen Erythrozyten. Über 90% der untersuchten Adenokarzinomgewebe besaßen T-spezifische immunreactive Strukturen, gemessen mithuman-anti-T Seren, im Gegensatz zu gesunden und gutartig veränderten Geweben. Bei Adenokarzinomträgern wird das karzinom-assoziierte T Antigen vom Organismus als fremd erkannt. Die verzögerte Hautüberempfindlichkeitsreaktion gegen T Antigen (DTHR-T) war in allen 25 Patienten mit Lungenadenokarzinom positiv, in 88% von 101 Patienten mit ductulärem, in 43% von 30 mit lobulärem oder tubulärem Mammakarzinom sowie in 9/9 Patienten mit Körperhöhlen-Adenokarzinomen. Alle 7 Patienten mit kleinzelligem Lungenkarzinom und 3/5 mit malignem Melanom reagierten positiv. Die DTHR-T war negativ in allen 17 Patienten mit malignen Hirntumoren, Leukämien, Hodgkin, Sarkom und Schilddrüsenkrebs. Die DTHR-T war spezifisch: alle 77 gesunden und 48/49 Personen mit nichtkrebsigen Erkrankungen einschließlich 23/24 Lungenpatienten hatten eine negative DTHR-T; ein Patient mit organisierender interstitieller Pneumonitis reagierte positiv; dies deutet auf eine mögliche Fehlerquelle hin. 91% von 149 Patienten, histologisch als gutartige Brusterkrankung diagnostiziert, hatten eine negative DTHR-T; die Histologie einiger positiv reagierender Patienten wurde reexaminiert und erwies sich in 2 Fällen als in situ Karzinom.

In vitro „Leukocyte migration inhibition“ und „scoring“ der anti-T Agglutinine ergaben eine korrekte Diagnose bei vielen Adenokarzinomen einschließlich 4 Fällen, die zur Zeit unserer positiven Resultate eine negative Histologie hatten, bei denen spätere Biopsien aber positiv ausfielen. Im allgemeinen waren die in vitro Teste weniger sensitiv und spezifisch als die DTHR-T.

Das T-anti-T System könnte sich auch zum „screening“ und „monitoring“ eignen. Chirurgische Entfernung des Primärkarzinoms führte zu einem „rebound“ des anti-T Titers in Brustkrebspatienten, erneuter Abfall wurde in einigen Fällen vor klinischem Rückfall beobachtet. Positive DTHR-T wurde wieder negativ in mehreren Fällen von Brustkrebs Stage I und II bzw. Lungenadenokarzinom T1–2 N0–1 M0; diese Patienten hatten in der folgenden Beobachtungszeit keinen klinischen Rückfall.

Schlüsselwörter

T Antigen und Karzinom Anti-T Antikörper und Karzinom Verzögerte Hautüberempfindlichkeit gegen karzinomassoziiertes T Antigen Adenokarzinom-assoziierte T Spezifität 

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References

  1. 1.
    Anglin JH Jr, Lerner MP, Nordquist RE (1977) Blood group-like activity released by human mammary carcinoma cells in culture. Nature 269:254–255PubMedGoogle Scholar
  2. 2.
    Bird GWG (1964) Anti-T in peanuts. Vox Sang 9:748–749Google Scholar
  3. 3.
    Black MM, Leis HP Jr, Shore B, Zachrau RE (1974) Cellular hypersensitivity to breast cancer. Cancer 33:952–958PubMedGoogle Scholar
  4. 4.
    Black MM, Speer FD (1959) Immunology of cancer. Surg Gynecol Obstet 109:105–116Google Scholar
  5. 5.
    Boccardi V, Attinà D, Girelli G (1974) Influence of orally administered antibiotics on anti-T agglutinin of normal subjects and cirrhotic patients. Vox Sang 27:268–272PubMedGoogle Scholar
  6. 6.
    Boyd W (1921) Tissue resistance in malignant disease. Surg Gynecol Obstet 32:306–310Google Scholar
  7. 7.
    Bray J, Lemieux RU, McPherson TA (1981) Use of a synthetic hapten in the demonstration of the Thomsen-Friedenreich (T) antigen on neuraminidase-treated human red blood cells and lymphocytes. J Immunol 126:1966–1969PubMedGoogle Scholar
  8. 8.
    Caselitz FH, Stein G (1953) Experimentelle Beiträge zum Problem der Hämagglutination nach Thomsen. Z Immun Forsch 110:165–184Google Scholar
  9. 9.
    Caspar M (1967) Johannes Kepler's Weltharmonik: Transl ofHarmonices Mundi (Linz, Austria, 1619). Oldenbourg, Muenchen, p 8Google Scholar
  10. 10.
    Codington JF, Sanford BH, Jeanloz RW (1972) Glycoprotein coat of the TA3 cell. Isolation and partial characterization of a sialic acid containing glycoprotein fraction. Biochem 11:2559–2564Google Scholar
  11. 11.
    Desai PR, Springer GF (1979) Biosynthesis of blood group T-, N-, and M-specific immunodeterminants on human erythrocyte antigens. J Immunogenet 6:403–417PubMedGoogle Scholar
  12. 12.
    Duncan W, Kerr GR (1976) The curability of breast cancer. Br Med J 2:781–783PubMedGoogle Scholar
  13. 13.
    Ehrlich P (1909) Über den jetzigen Stand der Karzinomforschung. Ned T Genesk 1:273–290Google Scholar
  14. 14.
    Fisher B (1976) Some thoughts concerning the primary therapy of breast cancer. In: Breast cancer: a multidisciplinary approach. Springer, Berlin, Heidelberg New York, pp 150–163Google Scholar
  15. 15.
    Fisher ER, Gregorio RM, Fisher B (1975) The pathology of invasive breast cancer. Cancer 36:1–85PubMedGoogle Scholar
  16. 16.
    Fournier vD, Weber E, Hoeffken W, Bauer M, Kubli F, Barth V (1980) Growth rate of 147 mammary carcinomas. Cancer 45:2198–2207PubMedGoogle Scholar
  17. 17.
    Friedenreich V (1930) The Thomsen hemagglutination phenomenon. Levin & Munksgaard, CopenhagenGoogle Scholar
  18. 18.
    Gallager HS (1977) View from the giant's shoulder. Cancer 40:185–194.PubMedGoogle Scholar
  19. 19.
    Gottschalk A (1960) The chemistry and biology of sialic acid and related substances. Cambridge University Press, Cambridge, p 98Google Scholar
  20. 20.
    Hauschka TS, Weiss L, Holdridge BA, Cudney TL, Zumpft M, Planinsek JA (1971) Karyotypic and surface features of murine TA3 carcinoma cells during immunoselection in mice and rats. J Natl Cancer Inst 47:343–359PubMedGoogle Scholar
  21. 21.
    Hirszfeld L, Halber W, Laskowski J (1930) Untersuchungen über die serologischen Eigenschaften der Gewebe. I. Mitteilung. Über gruppenspezifische Differenzierung der Normal- und Krebsgewebe. Z Immun Forsch Exp Ther 64:61–80Google Scholar
  22. 22.
    Hollinshead AC, Stewart THM, Herberman RB (1974) Delayed-hypersensitivity reactions to soluble membrane antigens of human malignant lung cells. J Natl Cancer Inst 52:327–338PubMedGoogle Scholar
  23. 23.
    Howard DR, Ferguson P, Batsakis JG (1981) Carcinoma-associated cytostructural antigenic alterations: detection by lectin binding. Cancer 47:2872–2877PubMedGoogle Scholar
  24. 24.
    Howard DR, Taylor CR (1980) An antitumor antibody in normal human serum: Reaction of anti-T with breast carcinoma cells. Oncology 37:142–148PubMedGoogle Scholar
  25. 25.
    Hughes LE, Lytton B (1964) Antigenic properties of human tumours: delayed cutaneous hypersensitivity reactions. Br Med J 209–212Google Scholar
  26. 26.
    Kabat EA (1968) Structural concepts in immunology and immunochemistry. Holt, Rinehart, Winston, Inc., New YorkGoogle Scholar
  27. 27.
    Kusama S, Spratt JS Jr, Donegan WL, Watson FK, Cunningham C (1972) The gross rates of growth of human mammary carcinoma. Cancer 30:594–599PubMedGoogle Scholar
  28. 28.
    Laurent JC, Noël P, Faucon M (1978) Expression of a cryptic cell surface antigen in primary cell cultures from human breast cancer. Biomedicine 29:260–261PubMedGoogle Scholar
  29. 29.
    Lehmann-Facius H (1931) Über gruppenspezifische und heterogene Strukturen in Lipoidantigenen bösartiger Geschwülste. Frkft Z Pathol 41:521–594Google Scholar
  30. 30.
    Limas C, Lange P (1980) Altered reactivity for A, B, H antigens in transitional cell carcinomas of the urinary bladder. Cancer 46:1366–1373PubMedGoogle Scholar
  31. 31.
    Lotan R, Skutelsky E, Danon D, Sharon N (1975) The purification, composition, and specificity of the anti-T lectin from peanut (Arachis hypogæa). J Biol Chem 250:8518–8523PubMedGoogle Scholar
  32. 32.
    Luner SJ, Wile AG, Sparks FC (1977) Antibody to T and Tn antigens in patients with breast cancer. Proc Am Assoc Cancer Res, Abstr 375Google Scholar
  33. 33.
    McCluskey RT, Benacerraf B, McCluskey JW (1963) Studies on the specificity of the cellular infiltrate in delayed hypersensitivity reactions. J Immunol 90:466–477PubMedGoogle Scholar
  34. 34.
    Newman RA, Klein P, Redland P (1979) Binding of peanut lectin to breast epithelium, human carcinomas, and a cultured rat mammary stem cell: Use of the lectin as a marker of mammary differentiation. J Natl Cancer Inst 63:1339–1346PubMedGoogle Scholar
  35. 35.
    Old LJ (1981) Cancer immunology: the search for specificity. GHA Clowes memorial lecture. Cancer Res 41:361–375PubMedGoogle Scholar
  36. 36.
    Ozzello L, Sanpitak P (1970) Epithelial-stromal junction of intraductal carcinoma of the breast. Cancer 26:1186–1198PubMedGoogle Scholar
  37. 37.
    Pereira MEA, Kabat EA, Lotan R, Sharon N (1976) Immunochemical studies on the specificity of the peanut (Arachis hypogaea) agglutinin. Carbohyd Res 51:107–118Google Scholar
  38. 38.
    Ray PK, Idiculla A, Mark R, Rhoads JE Jr, Thomas H, Bassett JG, Cooper DR (1981) Extracorporeal immunoadsorption of plasma from a metastatic colon carcinoma patient by protein A-containing non-viable staphylococcus aureus. Clinical, biochemical, serological, and histological evaluation of the patient's response. Cancer (in press)Google Scholar
  39. 39.
    Richerson HB, Dvorak HF, Leskowitz S (1970) Cutaneous basophil sensitivity, a new look at the Jones-Mote Reaction, general characteristics. J Exp Med 132:546–556PubMedGoogle Scholar
  40. 40.
    Rosenow EC, Carr DJ (1979) Bronchogenic carcinoma. Ca — A Cancer J Clinicians 29:233–245Google Scholar
  41. 41.
    Sams WM (1980) Necrotizing vasculitis. J Am Acad Dermatol 3:1–13PubMedGoogle Scholar
  42. 42.
    Scanlon EF (1981) The early diagnosis of breast cancer. Cancer 48:523–526PubMedGoogle Scholar
  43. 43.
    Sellei J (1981) The occurrence of Thomsen-Friedenreich receptors in bovine erythrocytes of various FV genotypes. J Immunogenet 8:263–269PubMedGoogle Scholar
  44. 44.
    Spencer H (1977) Pathology of the lung, vol 2. Saunders, Philadelphia, p 873Google Scholar
  45. 45.
    Springer GF (1971) Blood-group and Forssman antigenic determinants shared between microbes and mammalian cells. Prog Allergy 15:9–77PubMedGoogle Scholar
  46. 46.
    Springer GF (1977) Enzyme-treated erythrocytes and inhibition of hemagglutination by antibodies and antibody-like reagents in semiquantitative tube tests. In: Methods in immunology and immunochemistry, vol. 4. Academic Press, New York, pp 14–19, 67–72Google Scholar
  47. 47.
    Springer GF, Ansell NJ (1958) Inactivation of human erythrocyte agglutinogens M and N by influenza viruses and receptor-destroying enzyme. Proc Natl Acad Sci (USA) 44:182–189Google Scholar
  48. 48.
    Springer GF, Cantrell JL, Desai PR, Tegtmeyer H (1982) Human blood group M-, N-, T- and Tn-specific substances in lipidic extracts of line-10 hepatocarcinoma of Strain-2 guinea pigs. Clin Immunol Immunopathol 20, (in press)Google Scholar
  49. 49.
    Springer GF, Codington JF, Jeanloz RW (1972) Surface glycoprotein from a mouse tumor cell as specific inhibitor of antihuman blood-group N agglutinin. J Natl Cancer Inst 49:1469–1470PubMedGoogle Scholar
  50. 50.
    Springer GF, Desai PR (1974) Common precursors of human blood group MN specificities. Biochem Biophys Res Comm 61:470–475PubMedGoogle Scholar
  51. 51.
    Springer GF, Desai PR (1975) Human blood-group MN and precursor specificities: structural and biological aspects. Carbohyd Res 40:183–192Google Scholar
  52. 52.
    Springer GF, Desai PR (1977) Human blood group MN precursor specificities in enterobacteriaceae and their lipopolysaccharides. Am Soc Microbiol Ann Meet, Abstr 88Google Scholar
  53. 53.
    Springer GF, Desai PR (1974) Relation of human blood-groups MN to cancer cell surface antigens and to receptors for oncogenic viruses. Ann Clin Lab Sci 4:294–298PubMedGoogle Scholar
  54. 54.
    Springer GF, Desai PR, Banatwala I (1974) Blood group MN specific substances and precursors in normal and malignant human breast tissues. Naturwissenschaften 61:457–458Google Scholar
  55. 55.
    Springer GF, Desai PR, Banatwala I (1975) Blood group MN antigens and precursors in normal and malignant human breast glandular tissue. J Natl Cancer Inst 54:335–339PubMedGoogle Scholar
  56. 56.
    Springer GF, Desai PR, Murthy MS (1978) Letter to the Editor, Histochemical methods for the demonstration of Thomsen-Friedenreich antigen in cell suspensions and tissue sections. Klin Wochenschr 56:1225–1226PubMedGoogle Scholar
  57. 57.
    Springer GF, Desai PR, Murthy MS, Tegtmeyer H, Scanlon EF (1979) Human carcinoma-associated precursor antigens of the blood group MN system and the host's immune responses to them. Prog Allergy 26:42–96PubMedGoogle Scholar
  58. 58.
    Springer GF, Desai PR, Scanlon EF (1976) Blood group MN precursors as human breast carcinoma-associated antigens and “naturally” occurring human cytotoxins against them. Cancer 37:169–176PubMedGoogle Scholar
  59. 59.
    Springer GF, Desai PR, Schachter H, Narasimhan S (1976) Enzymatic synthesis of human blood group M-, N- and T-specific structures. Naturwissenschaften 63:488–489PubMedGoogle Scholar
  60. 60.
    Springer GF, Murthy MS, Desai PR, Scanlon EF (1980) Breast cancer patient's cell-mediated immune response to Thomsen-Friedenreich (T) antigen. Cancer 45:2949–2954PubMedGoogle Scholar
  61. 61.
    Springer GF, Nagai Y, Tegtmeyer H (1966) Isolation and properties of human blood group NN and meconium-Vg antigens. Biochemistry (NY) 5:3254–3272PubMedGoogle Scholar
  62. 62.
    Springer GF, Tegtmeyer H (1981) Origin of anti-Thomsen-Friedenreich (T) and Tn agglutinins in man and in White Leghorn chicks. Br J Haematol 47:453–460PubMedGoogle Scholar
  63. 63.
    Springer GF, Tegtmeyer H, Huprikar SV (1972) Anti-N reagents in elucidation of the genetical basis of human blood-group MN specificities. Vox Sang 22:325–343PubMedGoogle Scholar
  64. 64.
    Thatcher N, Hashmi K, Chang J, Swindell R, Crowther D (1980) Anti-T antibody in malignant melanoma patients. Cancer 46:1378–1382PubMedGoogle Scholar
  65. 65.
    Vaith P, Uhlenbruck G (1978) The Thomsen agglutination phenomenon: a discovery revisited 50 years later. Z Immun Forsch 154:1–14Google Scholar
  66. 66.
    Vincent RG, Pickren JW, Lane WW, Bross I, Takita H, Houten L, Gutierrez AC, Rzepka T (1977) The changing histopathology of lung cancer. Cancer 39:1647–1655PubMedGoogle Scholar
  67. 67.
    Weiser MM, Podolsky DK, Isselbacher KJ (1976) Cancer-associated iso-enzyme of serum galactosyltransferase. Proc Natl Acad Sci USA 73:1319–1322PubMedGoogle Scholar
  68. 68.
    Hashimoto T, Fukuoka M, Nagasawa S, Tamai S, Kusunoki Y, Kawahara M, Furuse K, Sawamura K, Fujimoto T (1979) Small cell carcinoma of the lung and its histological origin. Am J Surg Pathol 3:343–351PubMedGoogle Scholar
  69. 69.
    Churg A (1978) The fine structure of large cell undifferentiated carcinoma of the lung. Human Pathol 9:143:156Google Scholar
  70. 70.
    Miller RA, Levy R (1981) Response of cutaneous T cell lymphoma to therapy with hybridoma monoclonal antibody. Lancet 2:226–230PubMedGoogle Scholar
  71. 71.
    Ritz J, Pesando JM, Sallan SE, Clavell LA, Notis-McConarty J, Rosenthal P, Schlossman SF (1981) Serotherapy of acute lymphoblastic leukemia with monoclonal antibody. Blood 58:141–152PubMedGoogle Scholar
  72. 72.
    Tisserand-Jochem EM (1979) La polyagglutination des globules rouges, étude de deux types de polyagglutinabilité acquisé. These L'université Pierre et Marie Curie, ParisGoogle Scholar
  73. 73.
    Vos GH, Brain P (1981) Heterophile antibodies, immunoglobulin levels, and the evaluation of anti-T activity in cancer patients and controls. South Afr Med J 60:133–136Google Scholar
  74. 74.
    Vos GH, Rose EF, Vos D (1981) Antibody responses to T-activated red cells in children from high- and low-risk areas of cancer of the oesophagus in Transkei. South Afr Med J 59:56–60Google Scholar
  75. 75.
    Summers JL, Coon JS, Weinstein, RS, Rose M, Ward BS, Falor WH (1981) Prognostic significance of T antigen detection in urinary bladder carcinoma. Am Urol Assoc N Centr Sec 55:45Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • G. F. Springer
    • 1
    • 2
  • S. M. Murthy
    • 1
    • 2
  • P. R. Desai
    • 1
    • 2
  • W. A. Fry
    • 1
    • 2
  • H. Tegtmeyer
    • 1
    • 2
  • E. F. Scanlon
    • 1
    • 2
  1. 1.Immunochemistry Research, Thoracic Surgery, Department of SurgeryEvanston HospitalEvanstonUSA
  2. 2.Departments of Surgery and Microbiology-ImmunologyUniversityEvanstonUSA

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