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Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1988 Sep;27(2):163–170. doi: 10.1007/BF00200022

Comparative studies between in vitro and in vivo effects of human beta-interferon on natural killer activity and its relevance to immunochemotherapy

Stefania D'Atri 1, Maria Pia Fuggetta 1, Gabriella Giganti 2, Lucio Tentori 1, Mario Roselli 2, Corrado Nunziata 2, Simonetta Pastore 2, Enzo Bonmassar 2, Liana De Vecchis 2,
PMCID: PMC11038518  PMID: 3416325

Abstract

A good correlation was found between in vivo and in vitro responses of peripheral MNC from breast cancer patients and the NK boosting effect of human βIFN. In vitro immunochemotherapy studies showed that marked antitumor effects were obtained against cultured cancer cells when a widely used chemotherapeutic agent such as 5-FU was combined with nonsensitized spontaneously cytolytic MNC, preactivated in vitro with βIFN. These results suggest that the in vitro susceptibility assay of MNC to IFNs could be used for predicting favorable responses to immunochemotherapy regimens employing IFNs as immunomodulating agents.

Keywords: Breast Cancer, Cancer Cell, Cancer Patient, Cancer Research, Natural Killer

Footnotes

Abbreviations used: βIFN, beta-interferon; CM, complete medium; CTX, cyclophosphamide; E:T ratio, effector target ratio; EDTA, ethylenediaminetetraacetic acid; FCS, fetal calf serum; 5-FU, 5-fluorouracil; γIFN, gamma-interferon; Hepes, N-2-hydroxyethylpiperazine-N-2-ethanesulphonic acid IFNs, interferons; KC, killed cells; LDIF, low doses beta-interferon; LU, lytic unit; MAT macrotest; MIT, microtest; MNC, mononuclear cells; MNC/IFN, βIFN-pretreated MNC; MTX, methotrexate; NB, no boosting; NK, natural killer; NKA, NK activity; NR, natural resistance; PM, positive modulation; SE, standard error; WM, washing medium

References

  • 1.Bistoni F, Marconi P, Pitzurra M, Frati L, Spreafico F, Goldin A, Bonmassar E. Combined effects of BCG or Candida albicans (CA) with antitumor agents against a virus-induced lymphoma in mice. Eur J Cancer. 1979;15:1305. doi: 10.1016/0014-2964(79)90106-3. [DOI] [PubMed] [Google Scholar]
  • 2.Bonmassar E, Cudkowicz G, Vadlamudi S, Goldin A. Influence of tumor-host differences at a single histocompatibility locus (h-1) on the antileukemic effect of 1,3-bis(2-chloreoethyl)-1-nitrosourea (NSC-409962) Cancer Res. 1970;30:2538. [PubMed] [Google Scholar]
  • 3.Bonmassar E, Goldin A, Cudkowicz G. Differential reactivity of mice to alloantigens associated with the D and K end of H-2. Transplantion. 1971;12:314. doi: 10.1097/00007890-197110000-00014. [DOI] [PubMed] [Google Scholar]
  • 4.Bonmassar A, Houchens D, Iorio AM, Neri M, Santoni A, Goldin A. Soluble factors produced by normal or tumor cells inhibiting the uptake of 5-iodo-2-deoxy-uridine by cancer cells in vitro. Eur J Cancer. 1978;14:421. doi: 10.1016/0014-2964(78)90214-1. [DOI] [PubMed] [Google Scholar]
  • 5.Boyum A. Isolation of lymphocytes from human blood. Further observation. Scand J Clin Lab Invest. 1968;21:31. [PubMed] [Google Scholar]
  • 6.Clark EA, Harmon RC. Genetic control of natural cytotoxicity and hybrid resistance. Adv Cancer Res. 1980;31:227. doi: 10.1016/s0065-230x(08)60659-4. [DOI] [PubMed] [Google Scholar]
  • 7.Cudkowicz G, Hochman PS. Do natural killer cells engage in regulated reaction against self to ensure homeostasis? Immunol Rev. 1979;44:13. doi: 10.1111/j.1600-065x.1979.tb00266.x. [DOI] [PubMed] [Google Scholar]
  • 8.D'Atri S, Tentori L, Fuggetta MP, Marini S, Bonmassar E. A miniaturized cell-mediated cytotoxicity assay with human effector mononuclear cells. Int J Tissue React. 1986;8:383. [PubMed] [Google Scholar]
  • 9.Djeu JY, Heinbaugh JA, Viera WD, Holden HT, Herberman RB. The effect of immunopharmacological agents on mouse natural cell-mediated cytotoxicity and on its augmentation by PolyI:C. Immunopharmacology. 1979;1:231. doi: 10.1016/0162-3109(79)90040-7. [DOI] [PubMed] [Google Scholar]
  • 10.Gaffney EV. A cell line (HBL-100) established from human breast milk. Cell Tissue Res. 1982;227:563. doi: 10.1007/BF00204786. [DOI] [PubMed] [Google Scholar]
  • 11.Harmon RC, Clark EA, Toole CO, Wicker LS. Resistance of H-2 heterozygous mice to parental tumors. I. Hybrid resistance and natural cytotoxicity to EL-4 are controlled by the H-2D-Hh-1 region. Immunogenetics. 1977;4:601. [Google Scholar]
  • 12.Harrison DE, Carlson GA. Effects of beige mutation and irradiation on natural resistance to marrow grafts. J Immunol. 1983;130:484. [PubMed] [Google Scholar]
  • 13.Herberman RB, Ortaldo JR, Bonnard GD. Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature. 1979;277:221. doi: 10.1038/277221a0. [DOI] [PubMed] [Google Scholar]
  • 14.Iorio AM, Neri M, Enrico P, Goldin A, Bonmassar E. Combined effects of natural resistance and chemotherapy against a murine lymphoma in lethally-irradiated mice. Int J Cancer. 1981;28:497. doi: 10.1002/ijc.2910280416. [DOI] [PubMed] [Google Scholar]
  • 15.Judge SM, Chatterton RT. Progesterone-specific stimulation tryglyceride biosynthesis in a breast cancer cell line (T-470) Cancer Res. 1983;43:4407. [PubMed] [Google Scholar]
  • 16.Kiessling R, Hochman PS, Haller O, Shearer GM, Wigzell H, Cudkowicz G. Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol. 1977;7:655. doi: 10.1002/eji.1830070915. [DOI] [PubMed] [Google Scholar]
  • 17.Kiuchi Y. Strain difference in mouse natural killer activity augmented by mouse interferon and poly I.C. Jikken Dobutsu. 1986;35:239. doi: 10.1538/expanim1978.35.3_239. [DOI] [PubMed] [Google Scholar]
  • 18.Lindahl P, Leary P, Grener I. Enhancement by interferon of the specific cytotoxicity of sensitized lymphocytes. Proc Natl Acad Sci USA. 1972;69:721. doi: 10.1073/pnas.69.3.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Lotzova E. Analogy between rejection of hemopoietic transplants and natural killing. In: Herberman RB, editor. Natural cell-mediated immunity against tumors. New York: Academic Press; 1980. p. 1117. [Google Scholar]
  • 20.Lotzova E, Pollack SB, Savary CA. Direct evidence for the involvement of natural killer cells in bone marrow transplantation. In: Herberman RB, editor. NK cells and other natural effector cells. New York: Academic Press; 1982. p. 1535. [Google Scholar]
  • 21.Lozzio CB, Lozzio BB. Properties and usefulness of the original K562 human myelogenous leukemia cell line. Leuk Res. 1979;3:363. doi: 10.1016/0145-2126(79)90033-x. [DOI] [PubMed] [Google Scholar]
  • 22.Marth C, Daxenbichler G, Dapun O. Synergistic antiproliferative effect of human recombinant interferons and retinoic acid in cultured breast cancer cells. J Natl Cancer Inst. 1986;77:1197. [PubMed] [Google Scholar]
  • 23.Martin DS, Fugmann RA, Hayworth P. Surgery, cancer chemotherapy, host defences and tumor size. J Natl Cancer Inst. 1962;29:817. [Google Scholar]
  • 24.Mihich E. Combined effects of chemotherapy and immunity against leukemia L1210 in DBA/2 mice. Cancer Res. 1969;29:848. [PubMed] [Google Scholar]
  • 25.Moore M. Interferon and the immune system 2: effect of IFN on the immune system. In: Burke DC, Morris AG, editors. Interferons from molecular biology to clinical application. Cambridge: Cambridge University Press; 1983. p. 181. [Google Scholar]
  • 26.Oheler JR, Herberman RB. Natural cell-mediated cytotoxicity in rats. III Effects of immunopharmacological treatments on natural reactivity and on reactivity augmented by polyinosinic-polycytidylic acid. Int J Cancer. 1978;21:221. doi: 10.1002/ijc.2910210214. [DOI] [PubMed] [Google Scholar]
  • 27.Okumura K, Habu S, Shimamura K. The role of asialo GM1 (GA1) cells in the resistance to transplants of bone marrow or other tissue. In: Herberman RB, editor. NK cells and other natural effector cells. New York: Academic Press; 1982. p. 1527. [Google Scholar]
  • 28.Pastore S, De Vecchis L, Migliorati G, Giuliani A, Bonmassar E. Effect of Vincristine and Vindesine on NK-mediated cytolysis of human leukemic cells. Chemioterapia. 1982;1:318. [Google Scholar]
  • 29.Pastore S, De Vecchis L, Migliorati G, Frati L, Giuliani A, Bonmassar E. Influence of Vindesine on the lytic phase of mouse natural cytotoxicity against human leukemic cells. Int J Immunopharmacol. 1983;4:183. doi: 10.3109/08923978209026433. [DOI] [PubMed] [Google Scholar]
  • 30.Pearson JW, Pearson GR, Gibson WT, Cherman JC, Chirigos MA. Combined chemo-immunostimulation therapy against murine leukaemia. Cancer Res. 1972;32:904. [PubMed] [Google Scholar]
  • 31.Riccardi C, Bartocci A, Puccetti F, Spreafico F, Goldin A, Bonmassar E. Synergism between chemotherapy and antitumor allograft responses in intact or lethally irradiated mice. Fed Proc. 1977;36:281. [Google Scholar]
  • 32.Riccardi C, Bartocci A, Puccetti P, Spreafico F, Bonmassar E, Goldin A. Combined effects of antineoplastic agents and anti-lymphoma allograft reactions. Eur J Cancer. 1980;16:23. doi: 10.1016/0014-2964(80)90104-8. [DOI] [PubMed] [Google Scholar]
  • 33.Roder JC, Karre K, Kiessling R. Natural killer cells. Prog Allergy. 1981;28:66. [PubMed] [Google Scholar]
  • 34.Tentori L, Fuggetta MP, D'Atri S, Aquino A, Nunziata C, Roselli M, Ballatore P, Bonmassar E, De Vecchis L. Influence of low-dose beta-interferon on natural killer activity in breast cancer patients subjected to chemotherapy. Cancer Immunol Immunother. 1987;24:86. doi: 10.1007/BF00199838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Thorn RM, Herney CS. Kinetic analysis of target cell destruction by effector T cells. Delineation of parameters related to the frequency and lytic efficiency of killer cells. J Immunol. 1976;117:2213. [PubMed] [Google Scholar]
  • 36.Zarling JM, Sasman J, Eskra L, Borden EC, Horoszewicz JS, Carter WA. Enhancement of T cell cytotoxic responses by purified human fibroblast interferon. J Immunol. 1978;121:2002. [PubMed] [Google Scholar]

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