Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Lymphotoxin production by regional lymph node lymphocytes in patients with uterine cervical cancer


The cytotoxin production by regional lymph node cells was examined in 25 patients with uterine cervical cancer and 10 patients with uterine myoma. The patients in stage I had significantly increased spontaneous release of cytotoxins compared with that in stages II, III, and IV. The spontaneous release in stages III and IV was markedly reduced. There was no difference in the release of cytotoxins from peripheral blood lymphocytes between cancer patients and patients with myoma or healthy controls. The cytotoxin production by lymph node cells was increased in stage III by stimulating with formalin-fixed QG-K cells derived from uterine cervical cancer, but not in stages I and II. Almost all of the cytotoxic activity of cytotoxin was abrogated by antilymphotoxin antibody. However, the cytotoxin activity was partially inhibited by anti-tumor necrosis factor antibody. These results suggest that cytotoxins released from the regional lymph node cells of uterine cancer patients are derived from, most of all, lymphotoxin.

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


  1. 1.

    Flannery GR, Chalmers PJ, Rolland JM, Nairn RC: Immune response to a syngeneic rat tumour: Development of regional node lymphocyte anergy. Brt J Cancer 28:118–122, 1973

  2. 2.

    Goldfarb PM, Hardy MA: The immunologic responsiveness of regional lymphocytes in experimental cancer. Cancer 35:778–783, 1975

  3. 3.

    Koscielny MG, Le MG, Tubiana M: The natural history of human breast cancer. The relationship between involvement of axillary lymph nodes and the initiation of distant metastases. Br J Cancer 59:775–782, 1989

  4. 4.

    Tatake RJ, Krishnan, N, Rao RS, Fakih AR, Gangal SG: Lymphokine-activated killer-cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer. Int J Cancer 43:560–566, 1989

  5. 5.

    Nakamura H, Ishiguro K, Mori T: Different immune functions of peripheral blood, regional lymph node, and tumor infiltrating lymphocytes in lung cancer patients. Cancer 62:2489–2497, 1988

  6. 6.

    Micekl RA, Kessler DJ, Taylor JMG, Lichtenstein A: Natural killer cell cytotoxicity in the peripheral blood, cervical lymph nodes, and tumor of head and neck cancer patients. Cancer Res 48:5017–5022, 1988

  7. 7.

    Saxon A, Portis J: Lymphoid subpopulation changes in regional lymph nodes in squamous head and neck cancer. Cancer Res 37:1154–1158, 1977

  8. 8.

    Roubin R, Bekkoucha F, Fondaneche MC, Quan PC, Micheau CH, Cachin Y, Burtin P: Lymphoid cells in lymph nodes and peripheral blood of patients with squamous cell carcinoma of the head and neck. J Cancer Res Clin Oncol 102:277–287, 1982

  9. 9.

    Saxon A, Portaro J: Preservation of in vitro biological functions in regional lymph node lymphocytes in squamous head and neck cancer. Cancer Res 37:1159–1164, 1977

  10. 10.

    Lisafeld BA, Minowada J, Klein E, Holtermann OA: Lymphotoxins: Selective cytotoxic effects. Int Arch Allergy Appl Immunol 62:59–66, 1980

  11. 11.

    Matsunaga K, Mashiba H, Sagawa H, Jimi S, Watanabe Y, Kurano A, Saito T, Tomoda H, Furusawa M: Lymphotoxin activity of regional lymph nodes of cancer patients and its relation to stages of cancer and the regulatory role of macrophages. Invas Metastas 7:41–52, 1987

  12. 12.

    Khan A, Weldon D, Duvall J, Pitchyangkul S, Hill NO: A standardized automated computer assisted micro-assay for lymphotoxin.In Human Lymphokines, A Khan, O Hill (eds). New York, Academic Press, 1982, pp 23–30

  13. 13.

    Mashiba H, Matsunaga K, Jimi S, Watanabe Y, Kurano A, Saito T, Furusawa M: Macrophage activity of regional lymph nodes of cancer patients and its relation to stages of cancer. Invas Metastas 7:41–52, 1987

  14. 14.

    Harrington JT: Involvement of lymphocyte mediators in the rejection of a murine tumor allograft. Cell Immunol 30:261–271, 1977

  15. 15.

    Papermaster BW, Holtermann OA, Rosner D, Klein E, Dao T: Regressions produced in breast cancer lesions by a lymphokine fraction from a human lymphoid cell line. Res Commun Chem Pathol Pharmacol 8:413–416, 1974

  16. 16.

    Papermaster BW, Holtermann OA, McDaniel MC, Klein E, Djerassi I, Rosner D, Dao T, Costanzi JJ: Effect of supernatants from long-term lymphoid cell lines on metastatic cutaneous tumors following local injection. Ann NY Acad Sci 276:584–591, 1976

  17. 17.

    Anastassiades OT, Pryce DM: Immunological significance of the morphologic changes in lymph nodes draining breast cancer. Br J Cancer 20:239–249, 1966

  18. 18.

    Black MM, Freeman C, Mark T, Harvei S, Cuther SJ: Prognostic significance of microscopic structure of gastric carcinomas and their regional lymph nodes. Cancer 27:703–711, 1971

  19. 19.

    van Nagell JR Jr, Donaldson ES, Parker JC, van Dyke AH, Wood EG: The prognostic significance of pelvic lymph node morphology in carcinoma of the uterine cervix. Cancer 39:2624–2632, 1977

  20. 20.

    Veresio L, Holden HT: Suppression of lymphokine production. I. Macrophage-mediated inhibition of MIF production. Cell Immunol 56:16–28, 1980

  21. 21.

    Prakash SS, Reeves WC, Sisson GR, Brenes M, Goday J, Bacchetti S, de Britton RC, Rawls WE: Herpes simplex virus type 2 and human papillomavirus type 16 in cervicitis, dysplasia and invasive cervical carcinoma. Int J Cancer 35:51–57, 1985

  22. 22.

    Frenkel N, Roizman B, Cassai E, Nahmias A: A DNA fragment of herpes simplex 2 and its transcription in human cervical cancer tissue. Proc Natl Acad Sci (Wash) 69:3784–3789, 1972

  23. 23.

    Pfister H: Biology and biochemistry of papillomaviruses. Rev Physiol Biochem Pharmacol 99:112–181, 1984

  24. 24.

    van de Linde AW, Streefkerk M, Schuurman HJ, Velde ER, Kater L: Divergence between the occurrence of antibody and cellular immune reactivity to cervical carcinoma cell lines in preinvasive and macroinvasive stages of cervical carcinoma. Br J Cancer 47:147–153, 1983

  25. 25.

    Gifford GE, Flick DA: Natural production and release of tumour necrosis factor.In Tumour Factor and Related Cytotoxins, Foundation Symposium. New York, Willey, 1987, No. 131, pp 3–20.

  26. 26.

    Cuturi MC, Murphy M, Costa-Giomi MR, Weinmann R, Purussia B, Trinchieri G: Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med 165:1851–1594, 1987

  27. 27.

    Lee SH, Aggarwal BB, Rinderknecht E, Assisi F, Chiu H: The synergistic anti-proliferative effect of γ-interferon and human lymphotoxin. J Immunol 133:1083–1086, 1984

  28. 28.

    Williams TW, Bellanti JA: In vitro synergism between interferons and human lymphotoxin: Enhancement of lymphotoxin-induced target cell killing. J Immunol 130:518–520, 1983

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Matsunaga, K., Mashiba, H., Kurano, A. et al. Lymphotoxin production by regional lymph node lymphocytes in patients with uterine cervical cancer. J Clin Immunol 10, 265–272 (1990).

Download citation

Key words

  • Lymph node cells
  • lymphotoxin
  • tumor necrosis factor
  • formalin-fixed tumor cells
  • uterine cervical cancer