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. 1988 Oct;27(3):278–282. doi: 10.1007/BF00205452

Long-term influence of adjuvant therapy on natural killer cell activity in breast cancer

E Tichatschek 1, C C Zielinski 1, Ch Müller 1, P Sevelda 2, E Kubista 2, K Czerwenka 2, J Spona 2, H Wolf 3, M M Eibl 3
PMCID: PMC11038115  PMID: 2460239

Abstract

Unstimulated IFN- and IL2-stimulated (NK) cell activities were investigated in patients with breast cancer who had received either local radiotherapy alone or adjuvant chemotherapeutic treatment with CMF combined with radiotherapy 12 to 18 months previously. When tested against the primarily NK-sensitive K562 cell line, patients who had received adjuvant chemotherapeutic treatment with CMF were shown to have a significantly decreased unstimulated and IFN-stimulated NK cell activity, as compared to both patients after radiotherapy only (P<0.002) and P<0.005, respectively) and healthy control persons (P<0.05). The former group of patients also had a significantly decreased IFN-stimulated NK cell activity, when tested against the primarily NK-insensitive Chang hepatoma cell line, as compared to patients after radiotherapy only (P<0.005) and healthy controls (P<0.05). Moreover, patients after radiotherapy only proved to have a significantly increased unstimulated (P<0.01) and IFN-stimulated NK cell activity (K562: P<0.05; Chang hepatoma cell line: P<0.05), as compared to healthy control individuals. In contrast, no difference in IL2-stimulated NK cell activity was detected. The investigation for the expression of CD3 and/or Leu 19 antigens as phenotypic markers of cells with non-MHC restricted cytotoxicity showed a significantly lower percentage of cells with the CD3+ phenotype in patients with breast cancer, irrespective of the chosen post-operative treatment, as compared to healthy controls (P<0.01). Finally, patients with breast cancer who had received radiotherapy only had a significant trend towards an increased percentage of CD3+/Leu 19+ PMNC, as compared to both patients after CMF treatment (P<0.05) and healthy controls (P<0.025). We conclude that patients with breast cancer vary on a long-term basis in their NK activity and in the phenotype of their PMNC depending on their post-operative adjuvant management.

Keywords: Breast Cancer, Natural Killer, Natural Killer Cell, K562 Cell, Control Person

Abbreviations

NK

natural killer cells

IFN

interferon

IL 2

interleukin 2

CMF

cyclophosphamide, methotrexate, fluorouracil

ER

oestrogen receptor

PMNC

peripheral blood mononuclear cells

MHC

major histocompatibility complex

CTL

cytotoxic T lymphocytes

References

  • 1.Abruzzo LV, Rowley DA. Homeostasis of the antibody response: Immunoregulation by NK cells. Science. 1983;222:581–585. doi: 10.1126/science.6685343. [DOI] [PubMed] [Google Scholar]
  • 2.Abruzzo LV, Mullen CA, Rowley DA. Immunoregulation by natural killer cells. Cell Immunol. 1986;98:266–278. doi: 10.1016/0008-8749(86)90287-x. [DOI] [PubMed] [Google Scholar]
  • 3.Berenbaum MC (1974) Effects of cytotoxic drugs and ionizing radiation on immune responses. In: Stoll BA (ed) Host defence in breast cancer. Year Book Medical Publishers, p 147
  • 4.Blomgren H, Baral E, Edsmyr F, Strender LE, Petrini B, Wasserman J. Natural killer activity in peripheral lymphocyte population following local radiation therapy. Acta Radiol Oncol. 1980;19:139. doi: 10.3109/02841868009130145. [DOI] [PubMed] [Google Scholar]
  • 5.Bonadonna G, Rossi A, Valagussa P. Adjuvant chemotherapy in operable breast cancer: Ten years later. Lancet. 1985;I:976–977. doi: 10.1016/s0140-6736(85)91740-4. [DOI] [PubMed] [Google Scholar]
  • 6.Borden E. Interferons: rationale for clinical trials in neoplastic disease. Ann Intern med. 1979;91:472–479. doi: 10.7326/0003-4819-91-3-472. [DOI] [PubMed] [Google Scholar]
  • 7.Cunningham-Rundles S, Fillipa Da, Braun DW, et al. Natural cytotoxicity of peripheral blood lymphocytes and regional lymph node cells in breast cancer in women. J Natl Cancer Inst. 1981;67:585–590. [PubMed] [Google Scholar]
  • 8.Djeu JY, Heinbaugh JA, Holden HT, Herberman RB. Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol. 1979;122:175–188. [PubMed] [Google Scholar]
  • 9.Frydecka I, Blok K, Kornafel J, Kuliczkowaski K, Polakowska A. Early effects of radium therapy on natural killer activity in patients with gynaecological malignancies. Folia Haematol. 1986;113:499. [PubMed] [Google Scholar]
  • 10.Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon: Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982;155:1823–1841. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Hanna N, Burton RC. Definitive evidence that natural killer cells inhibit experimental tumor metastasis in vivo. J Immunol. 1981;127:1754–1758. [PubMed] [Google Scholar]
  • 12.Harris J, Sengar D, Stewart T, Hyslop D. The effect of immunosuppressive chemotherapy on immune function in patients with malignant disease. Cancer. 1976;37:1058–1067. doi: 10.1002/1097-0142(197602)37:2+<1058::aid-cncr2820370813>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  • 13.Heppner GH, Calabresi P. Selective suppression of humoral immunity by antineoplastic drugs. Annu Rev Pharmacol Toxicol. 1976;16:367–375. doi: 10.1146/annurev.pa.16.040176.002055. [DOI] [PubMed] [Google Scholar]
  • 14.Herberman RB, Ortaldo JR. Natural killer cells: Their role in defenses against disease. Science. 1981;214:24–29. doi: 10.1126/science.7025208. [DOI] [PubMed] [Google Scholar]
  • 15.Lanier LL, Le AM, Cwirla S, Federspiel N, Phillips JH. Antigenic, functional, and molecular genetic studies of human natural killer cells and cytotoxic T lymphocytes not restricted by the major histocompatibility complex. Fed Proc. 1986;45:2823–2828. [PubMed] [Google Scholar]
  • 16.Levy S, Herberman R, Maluish A, et al. Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters. Health Phys. 1985;4:99–113. doi: 10.1037//0278-6133.4.2.99. [DOI] [PubMed] [Google Scholar]
  • 17.Levy S, Herberman R, Maluish A, et al. Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters. Health Phys. 1985;4:99–113. doi: 10.1037//0278-6133.4.2.99. [DOI] [PubMed] [Google Scholar]
  • 18.Levy S, Herberman R, Lippman M, d'Angelo T. Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer. J Clin Oncol. 1987;5:348–353. doi: 10.1200/JCO.1987.5.3.348. [DOI] [PubMed] [Google Scholar]
  • 19.Levy S, Herberman R, Lippman M, d'Angelo T. Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer. J Clin Oncol. 1987;5:348–353. doi: 10.1200/JCO.1987.5.3.348. [DOI] [PubMed] [Google Scholar]
  • 20.Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–275. [PubMed] [Google Scholar]
  • 21.Müller C, Kalinowska W, Pohanka E, et al. Lytic effector cell function following kidney transplantation. Transplant Proc. 1987;19:2932–2938. [PubMed] [Google Scholar]
  • 22.Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastasic cancer. N Engl J Med. 1985;313:1485–1492. doi: 10.1056/NEJM198512053132327. [DOI] [PubMed] [Google Scholar]
  • 23.Rosenberg SA, Spiess P, Lafreniere R. New approach to the adoptive immunotherapy of cancer with tumour-infiltrating lymphocytes. Science. 1986;233:1318–1321. doi: 10.1126/science.3489291. [DOI] [PubMed] [Google Scholar]
  • 24.Schwartz RS, Eisner A, Dameshek W. The effect of 6-mercaptopurine on primary and secondary immune responses. J Clin Invest. 1959;38:1394–1403. doi: 10.1172/JCI103915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Spona J, Ulm R, Bieglmayer C, Husslein P. Hormone serum levels and hormone receptor contents of endometria in women with normal menstrual cycles and patients bearing endometrial carcinoma. Gynecol Obstet Invest. 1979;10:71–80. doi: 10.1159/000299920. [DOI] [PubMed] [Google Scholar]
  • 26.Welsh RM. Regulation of virus infections by natural killer cells. Nat Immun Cell Growth Regul. 1986;5:169–199. [PubMed] [Google Scholar]
  • 27.White D, Jones DB, Cooke T, Kirkham N. Natural killer (NK) activity in peripheral blood lymphocytes of patients with benign and malignant breast disease. Br J Cancer. 1982;46:611–616. doi: 10.1038/bjc.1982.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Zielinski CC, Kubista E, Salzer H, et al. Adjuvant chemotherapy combined with tamoxifen in postmenopausal patients with stage II breast cancer. Lancet. 1986;II:1164. doi: 10.1016/s0140-6736(86)90577-5. [DOI] [PubMed] [Google Scholar]
  • 29.Zielinski CC, Stuller I, Dorner F, et al. Impaired primary, but not secondary, immune response in breast cancer patients under adjuvant chemotherapy. Cancer. 1986;58:1648–1652. doi: 10.1002/1097-0142(19861015)58:8<1648::aid-cncr2820580812>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]

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