Abstract
We have investigated the effect of interferon β (INFß) on the natural killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) from patients with superficial and infiltrative transitional-cell carcinoma of the bladder (TCC) against both NK-sensitive and NK-resistant target cells. The normal NK activity found in PBMC from these patients can be significantly enhanced by short-term incubation (18 h) with INFß (P<0.05). The depressed NK cytotoxic activity found in PBMC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term incubation with INFß (P<0.05). In kinetic studies we found that the maximal levels of the INFß-promoted cytotoxic activity against NK-sensitive and against NK-resistant target cells in PBMC from TCC patients were reached after 18 h of culture. Short-term-INFß-incubated PBMC from patients with TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. The effector cells of the INFß-induced cytotoxic activity in PBMC from patients with TCC were CD16+ CD3− NK cells. This cytotoxic inducer effect of INFß synergized with that of interleukin-2. In conclusion, INFß can enhance the NK activity of PMBC from patients with TCC of the bladder.
Key words: Transitional cell carcinoma, Natural killer cytotoxic activity, Interferon β
References
- 1.Alvarez-Mon M, Casas J, Laguna R, Toribio ML, Ortiz de Landazuri M, Durantez A. Lymphokine induction of NK-like cytotoxicity in T cells from B-CLL. Blood. 1986;67:228. [PubMed] [Google Scholar]
- 2.Bonilla F, Alvarez-Mon M, Merino F, de la Hera A, Ales JE, España P, Durantez A. Interleukin 2 induces cytotoxic activity in lymphocytes from regional axillary nodes of breast cancer patients. Cancer. 1988;61:629. doi: 10.1002/1097-0142(19880215)61:4<629::aid-cncr2820610402>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- 3.Carballido J, Alvarez-Mon M. Immunoterapia con interferon alfa 2b intravesical en neoplasias uroteliales superficiales. Bases experimentales y clínicas. Madrid: Schering-Plough; 1991. [Google Scholar]
- 4.Carballido J, Alvarez-Mon M, Solovera J, Menendez-Ondina L, Durantez A. Clinical signification of NK activity in patients with TCC of the bladder. J Urol. 1990;143:29. doi: 10.1016/s0022-5347(17)39854-3. [DOI] [PubMed] [Google Scholar]
- 5.Carballido J, Moltó L, Manzano L, Olivier C, Salmerón O, Alvarez-Mon M. Interferon-alpha-2b enhances the natural killer activity of patients with transitional cell carcinoma of the bladder. Cancer. 1993;72:1743. doi: 10.1002/1097-0142(19930901)72:5<1743::aid-cncr2820720538>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- 6.Friedman RM. Immunophysiology. The role of cells and cytokines in immunity and inflammation. Oxford: Oxford University Press; 1991. Interferons; p. 194. [Google Scholar]
- 7.Glasham RW. A randomized controlled study of intravesical alpha 2b interferon in carcinoma in situ of the bladder. J Urol. 1990;144:658. doi: 10.1016/s0022-5347(17)39547-2. [DOI] [PubMed] [Google Scholar]
- 8.Grimm EA, Mazumder A, Zang 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. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Heo DS, Whiteside TL, Kanbour A, Herberman RB. Lymphocytes infiltrating human ovarian tumors. 1. Role of leu 19 (NKH1)-positive recombinant IL-2-activated cultures of lymphocytes infiltrating human ovarian tumors. J Immunol. 1988;140:4042. [PubMed] [Google Scholar]
- 10.Hermanek P, Sobin LH. TNM classification of malignant tumors. International union against cancer. 4th edn. Berlin Heidelberg New York: Springer; 1987. [Google Scholar]
- 11.Horoszewicz JS, Murphy GP. An assessment of the current use of human interferons in therapy of urological cancers. J Urol. 1989;142:1173. doi: 10.1016/s0022-5347(17)39022-5. [DOI] [PubMed] [Google Scholar]
- 12.Kadish AS, Doyle AT, Steinhauer EH, Ghossein NA. Natural cytotoxicity and interferon production in human cancer. Deficient natural killer activity and normal interferon production in patients with advanced disease. J Immunol. 1981;127:1817. [PubMed] [Google Scholar]
- 13.Lotze ME, Grimm EA, Mazumder A, Strauer J, Rosenberg SA. Lysis of fresh and cultured autologous tumor cells by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1982;41:4420. [PubMed] [Google Scholar]
- 14.Morales A, Ottenhof PC. Clinical application of a whole blood assay for human natural killer cell activity. Cancer. 1983;52:667. doi: 10.1002/1097-0142(19830815)52:4<667::aid-cncr2820520417>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- 15.Mukherji B, Chakraborty NG, Sivanandham M. T-cell clones that react against autologous human tumors. Immunol Rev. 1990;116:35. doi: 10.1111/j.1600-065x.1990.tb00803.x. [DOI] [PubMed] [Google Scholar]
- 16.Niijima T, et al. Intravesical treatment of bladder cancer with recombinant human interferon β. Cancer Immunol Immunother. 1989;30:81. doi: 10.1007/BF01665957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Ortaldo JR, Herberman RB. Heterogeneity of natural killer cells. Annu Rev Immunol. 1984;2:359. doi: 10.1146/annurev.iy.02.040184.002043. [DOI] [PubMed] [Google Scholar]
- 18.Paucker K, Cantell K, Henle W. Quantitative studies on viral interference in suspended cells. III. Effect of interferon viruses and interferon on the growth rate of cells. Virology. 1962;17:324. doi: 10.1016/0042-6822(62)90123-x. [DOI] [PubMed] [Google Scholar]
- 19.Raghavan D, Shipley WU, Garnick MB, Russell PJ, Richie PJ. Biology and management of bladder cancer. N Engl J Med. 1990;322:1129. doi: 10.1056/NEJM199004193221607. [DOI] [PubMed] [Google Scholar]
- 20.Rosenberg SA, Lotze MT, Muul LM, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin 2 or high doses of interleukin 2 alone. N Engl J Med. 1987;316:889. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
- 21.Sancho L, de la Hera A, Casas J, Vaquer S, Martinez-A C, Alvarez-Mon M. Two different maturational stages of natural killer lymphocytes in human newborn infants. J Pediatr. 1991;119:446. doi: 10.1016/s0022-3476(05)82061-x. [DOI] [PubMed] [Google Scholar]
- 22.Vaquer S, de la Hera A, Jordá J, Martinez-A C, Escudero M, Alvarez-Mon M. Diminished natural killer activity in pregnancy: modulation by interleukin 2 and interferon gamma. Scand J Immunol. 1987;26:691. doi: 10.1111/j.1365-3083.1987.tb02305.x. [DOI] [PubMed] [Google Scholar]
- 23.Witjes JA, Debrugne FMJ. Optimal management of superficial bladder cancer. Eur J Cancer. 1991;27:330. doi: 10.1016/0277-5379(91)90541-k. [DOI] [PubMed] [Google Scholar]
