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

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

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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.

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.

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Authors and Affiliations

  1. Immunochemistry Research, Thoracic Surgery, Department of Surgery, Evanston Hospital, 60201, Evanston, Il, USA

    G. F. Springer M.D., S. M. Murthy, P. R. Desai, W. A. Fry, H. Tegtmeyer & E. F. Scanlon

  2. Departments of Surgery and Microbiology-Immunology, University, 60201, Evanston, II, USA

    G. F. Springer M.D., S. M. Murthy, P. R. Desai, W. A. Fry, H. Tegtmeyer & E. F. Scanlon

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  1. G. F. Springer M.D.
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  2. S. M. Murthy
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  3. P. R. Desai
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  4. W. A. Fry
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  5. H. Tegtmeyer
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Dedicated to H.M.S., who courageously lived from age 48 through 54 with bilateral mastectomies for primary cancers, volunteered throughout 6 years invaluable participation in unestablished immunological procedures, and died with dignity of carcinomatosis

Supported by U.S. Public Health Service Grants CA 19083 and CA 22540, American Cancer Society Research Development Program Grant RD-133, a gift from the Mobil fndn. and Cancer Res. Inst. N.Y. G.F.S. is Julia S. Michels Investigator in Surgical Oncology

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Springer, G.F., Murthy, S.M., Desai, P.R. et al. Patients' immune response to breast and lung carcinoma-associated thomsen-friedenreich (T) specificity. Klin Wochenschr 60, 121–131 (1982). https://doi.org/10.1007/BF01711276

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